Nucleic acids encoding EPH-like receptor protein tyrosine kinases

ABSTRACT

Four novel members of the EPH sub-family of receptor protein tyrosine kinases are disclosed. Nucleic acid sequences encoding receptor proteins, recombinant plasmids and host cells for expression, and methods of producing and using such receptors are also disclosed.

This application is a continuation of application Ser. No. 08/229,509, filed Apr. 15, 1994, now abandoned, which is hereby incorporated by reference.

FIELD OF THE INVENTION

The invention relates generally to receptor protein tyrosine kinases (PTKs) and particularly to novel Eph-like receptor PTKs, to fragments and analogs thereof, and to nucleic acids encoding same. The present invention also relates to methods of producing and using such receptors.

BACKGROUND OF THE INVENTION

Receptor PTKs are a structurally related family of proteins that mediate the response of cells to extracellular signals (Ullrich et al. Cell 61, 203-212 (1990)). These receptors are characterized by three major functional domains: an intracellular region containing the sequences responsible for catalytic activity, a single hydrophobic membrane-spanning domain, and a glycosylated extracellular region whose structure determines ligand binding specificity. Signal transduction is initiated by the binding of growth or differentiation factors to the extracellular domain of their cognate receptors. Ligand binding facilitates dimerization of the receptor which can induce receptor autophosphorylation. Both soluble and membrane-associated protein ligands have been shown to function in this manner. This process is the initial step in a cascade of interactions involving the phosphorylation of a variety of cytoplasmic substrates and culminating in a biological response by the cell. The best characterized response to tyrosine kinase receptor activation is cell growth. However, analysis of the role of some growth factors in vivo suggests that differentiation or cell survival might also be mediated by tyrosine kinase receptor/ligand interactions.

Receptor PTKs have been grouped into fairly well-defined families on the basis of both sequence homology and shared structural motifs. The amino acid sequence of the portion of the intracellular domain responsible for the catalytic activity is well conserved among all tyrosine kinases and even more closely matched within a receptor sub-family. Comparisons of this portion of the amino acid sequence have been used to construct phylogenetic trees depicting the relatedness of family members to each other and to the tyrosine kinases as a whole (Hanks and Quinn, Methods Enzymol. 200, 38-62 (1991)). This sequence conservation has also been exploited in order to isolate new tyrosine kinases using the polymerase chain reaction (PCR)(Wilks, Proc. Natl. Acad. Sci. USA 86, 1603-1607 (1989)). Oligonucleotides based on the highly conserved catalytic domain of PTKs can be used as PCR primers to amplify related sequences present in the template. These fragments can then be used as probes for isolation of the corresponding full-length receptor clones from cDNA libraries. Anti-phosphotyrosine antibodies have also been used to identify PTK cDNA clones in phage expression libraries (Lindberg and Pasquale, Methods Enzymol. 200, 557-564 (1991)). These strategies have been used by a number of investigators to identify an ever-increasing number of protein tyrosine kinase receptors.

There are now 51 distinct PTK receptor genes that have been published and divided into 14 sub-families. One such sub-family is the EPH-like receptors. The prototype member, EPH, was isolated by Hirai et.al. (Science 238, 1717-1720 (1987)) using low stringency hybridization to a probe derived from the viral oncogene v-fps. EPH-like receptors have been implicated in cell growth based in part on studies which show that overexpression of the gene in NIH3T3 cells causes focus formation in soft agar and tumors in nude mice (Maru et al. Oncogene 5, 199-204 (1990)). Other members of the EPH sub-family which have been identified include the following:

ECK (Lindberg et al. Mol. Cell. Biol. 10, 6316-6324 (1990))

Elk (Lhotak et al. Mol. Cell. Biol. 11, 2496-2502 (1991))

Ceks 4,5,6,7,8,9, and 10 (Pasquale, Cell Regulation 2, 523-534 (1991); Sajjadi et al. The New Biologist 3, 769-778 (1991); Sajjadi and Pasquale Oncogene 8, 1807-1813 (1993))

HEK2 (Bohme et al. Oncogene 8, 2857-2862 (1993))

Eek, Erk (Chan and Watt, Oncogene 6, 1057-1061 (1991))

Ehk1, Ehk2 (Maisonpierre et al. Oncogene 8, 3277-3288 (1993))

Homologs for some of these receptors have been identified in other species (Wicks et al. Proc. Natl. Acad. Sci. USA 89, 1611-1615 (1992)); Gilardi-Hebenstreit et al. Oncogene 7, 2499-2506 (1992)). The expression patterns and developmental profiles of several family members suggest that these receptors and their ligands are important for the proliferation, differentiation and maintenance of a variety of tissues (Nieto et al. Development 116, 1137-1150 (1992)). Structurally, EPH sub-family members are characterized by an Ig-like loop, a cysteine rich region, and two fibronectin-type repeats in their extracellular domains. The amino acid sequences of the catalytic domains are more closely related to the SRC sub-family of cytoplasmic PTKs than to any of the receptor PTKs. Among the catalytic domains of receptor PTKs, the EPH sub-family is most similar in amino acid sequence to the epidermal growth factor receptor sub-family.

It is an object of the invention to identify novel receptors belonging to the EPH sub-family. A directed PCR approach has been used to identify five human EPH-like receptors from a human fetal brain cDNA library. These receptors are designated HEK4, HEK5, HEK7, HEK8, and HEK11. The relationship of these receptors to previously identified EPH-like receptors is as follows:

HEK4 is the human homolog of Cek4 (chicken) and Mek4 (mouse) and is identical to HEK (Boyd et al. J. Biol. Chem. 267, 3262-3267 (1992); Wicks et al., 1992) which was previously isolated from a human lymphoid tumor cell line.

HEK5 is the human homolog of Cek5, a full-length eph-like receptor clone from chicken. A portion of the HEK5 sequence was previously disclosed as ERK, a human clone encoding about sixty amino acids (Chan and Watt, 1991)

HEK7 is the human homolog of Cek7 isolated from chicken.

HEK8 is the human homolog of Cek8 a full-length clone from chicken and Sek, a full-length clone from mouse. (Nieto et al., 1992; Sajjadi et al., 1991)

HEK11 does not have a known non-human homolog. With the addition of the new members HEK5, HEK7, HEK8 and HEK11 and the report of a PCR fragment encoding an eph-like receptor (Lai & Lemke Neuron 6, 691-704 (1991)), a total of twelve distinct sequences that represent EPH-like receptors have been published, making it the largest known sub-family of PTKs.

It is a further object of the invention to generate soluble EPH-like receptors and antibodies to EPH-like receptors. Soluble receptors and antibodies are useful for modulating EPH-like receptor activation.

SUMMARY OF THE INVENTION

The present invention provides novel EPH-like receptor protein tyrosine kinases. More particularly, the invention provides isolated nucleic acids encoding four novel members of the sub-family of EPH-like receptor PTKs which are referred to collectively as HEKs (human-eph like kinases). Also encompassed are nucleic acids which hybridize under stringent conditions to EPH-like receptor nucleic acids. Expression vectors and host cells for the production of receptor polypeptides and methods of producing receptors are also provided.

Isolated polypeptides having amino acid sequences of EPH-like receptors are also provided, as are fragments and analogs thereof. Antibodies specifically binding the polypeptides of the invention are included. Also comprehended by the invention are methods of modulating the endogenous activity of an EPH-like receptor and methods for identifying receptor ligands.

DESCRIPTION OF THE FIGURES

FIG. 1 shows the nucleotide and predicted amino acid sequence of the HEK5 receptor (SEQ ID NO: 10 and SEQ ID NO: 11).

FIG. 2 shows the nucleotide and predicted amino acid sequence of the HEK7 receptor (SEQ ID NO: 12 and SEQ ID NO: 13).

FIG. 3 shows the nucleotide and predicted amino acid sequence of the HEK8 receptor (SEQ ID NO: 14 and SEQ ID NO: 15).

FIG. 4 shows the nucleotide and predicted amino acid sequence of the HEK11 receptor (SEQ ID NO: 16 and SEQ ID NO: 17).

FIG. 5 shows the comparison of the amino acid sequences of the human EPH receptor sub-family. The multiple sequence alignment was done using the LineUp program included in the Genetics Computer Group sequence analysis software package (Genetics Computer Group, (1991), Program Manual for the GCG Package, Version 7, April 1991, Madison, Wis., USA 53711). Dots indicate spaces introduced in order to optimize alignment. The predicted transmembrane domains and signal sequences of each receptor are indicated by underlining and italics, respectively. Cysteine residues conserved throughout the sub-family are indicated with asterisks. Arrows indicate the tyrosine kinase catalytic domain. Amino acid sequences of EPH, ECK and HEK2 were taken from the appropriate literature references.

FIG. 6 shows the molecular phylogeny of the EPH sub-family of receptor protein tyrosine kinases. Catalytic domain sequences were analyzed as described by Hanks and Quinn, 1991. The scale bar represents an arbitrary evolutionary difference unit. The EPH branch, which has been shown with a discontinuity for the sake of compactness, is 23.5 units in length.

FIGS. 7-11 show Northern blot analyses of the tissue distribution of the HEK receptors. Receptor cDNA probes, labeled with ³² P, were hybridized to either 2 μg of poly A⁺ RNA from human tissues (panel A, Clontech) or 10 μg of total RNA from rat tissues (panel B). Sizes of the transcripts were determined by comparison with RNA molecular weight markers (Bethesda Research Labs, Gaithersburg, Md.). FIG. 7, HEK4; FIG. 8, HEK5; FIG. 9, HEK7; FIG. 10; HEK8; FIG. 11; HEK 11.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to novel EPH-like receptor protein tyrosine kinases. More particularly, the invention relates to isolated nucleic acids encoding four novel members of the sub-family of EPH-like receptor PTKs. These four members are designated herein as HEK (human eph-like kinases). Nucleic acids encoding HEK receptors were identified in a human fetal brain cDNA library using oligonucleotide probes to conserved regions of receptor PTKs and EPH-like receptor PTKs. The predicted amino acid sequences of three HEK receptors had extensive homology in the catalytic domain to previously identified EPH-like receptors Cek5, Cek7 and Cek8 isolated from chicken and, accordingly, are designated HEK5, HEK7 and HEK8. The predicted amino acid sequence of the fourth HEK receptor revealed that it was not a homolog of any previously identified EPH-like receptor. It is designated HEK11. It is understood that the term "HEKs" comprises HEK5, HEK7, HEK8 and HEK11 as well as analogs, variants, and mutants thereof which fall within the scope of the invention.

The invention encompasses isolated nucleic acids selected from the group consisting of:

(a) the nucleic acids set forth in any of SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, or SEQ ID NO: 16 and their complementary strands;

(b) a nucleic acid hybridizing to the coding regions of the nucleic acids in any of SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, or SEQ ID NO: 16 under stringent conditions; and

(c) a nucleic acid of (b) which, but for the degeneracy of the genetic code, would hybridize to the coding regions of the nucleic acids in any of SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, or SEQ ID NO: 16. The nucleic acids of the invention preferably hybridize to HEK5, HEK7, HEK8, or HEK11 coding regions under conditions allowing up to about 5% nucleotide mismatch based upon observed nucleic acid identities among known human or nonhuman EPH-like receptors. An example of such a condition is hybridization at 60° in 1M Na⁺ followed by washing at 60° in 0.2×SSC. Other hybridization conditions may be ascertained by one skilled in the art which allow base pairing with similar levels of mismatch.

In a preferred embodiment, the isolated nucleic acids encode polypeptides having the amino acid sequences of HEK5, HEK7, HEK8 or HEK11. A nucleic acid includes cDNA, genomic DNA, synthetic DNA or RNA. Nucleic acids of this invention may encode full-length receptor polypeptides having an extracellular ligand-binding domain, a transmembrane domain, and a cytoplasmic domain, or may encode fragments such as extracellular domains which are produced in a soluble, secreted form. Nucleic acid constructs which produce soluble HEK receptors are described in Example 3. Polypeptides and fragments encoded by the nucleic acids have at least one of the biological activities of an EPH-like receptor protein tyrosine kinase, such as the ability to bind ligand.

The invention also encompasses nucleic acids encoding chimeric proteins wherein said proteins comprise part of the amino acid sequence of a HEK receptor linked to an amino acid sequence from a heterologous protein. One example of such a chimeric protein is an extracellular domain of a HEK receptor fused to a heterologous receptor cytoplasmic domain. Example 5 describes the construction and expression of a chimeric receptor comprising the HEK8 extracellular domain with the trkB cytoplasmic domain and a second chimeric receptor comprising the HEK11 extracellular domain with the trkB cytoplasmic domain. HEK receptors may also be fused to other functional protein domains, such as an Ig domain which acts as an antibody recognition site.

The nucleic acids of the present invention may be linked to heterologous nucleic acids which provide expression of receptor PTKs. Such heterologous nucleic acids include biologically functional plasmids or viral vectors which provide genetic elements for transcription, translation, amplification, secretion, etc. One example of an expression vector suitable for producing EPH-like receptors of the present invention is pDSRα which is described in Example 3. It is understood that other vectors are also suitable for expression of EPH-like receptors in mammalian, yeast, insect or bacterial cells. In addition, in vivo expression of nucleic acids encoding EPH-like receptor PTKs is also encompassed. For example, tissue-specific expression of EPH-like receptors in transgenic animals may be readily effected using vectors which are functional in selected tissues.

Host cells for the expression of EPH-like receptor PTKs will preferably be established mammalian cell lines, such as Chinese Hamster Ovary (CHO) cells or NIH 3T3 cells, although other cell lines suitable for expression of mammalian genes are readily available and may also be used. Such host cells are transformed or transfected with nucleic acid constructs suitable for expression of an EPH-like receptor. Transformed or transfected host cells may be used to produce suitable quantities of receptor for diagnostic or therapeutic uses and to effect targeted expression of EPH-like receptors in selected adult tissues, such as brain, kidney, and liver, or in embryonic or rapidly dividing tissues.

The present invention provides purified and isolated polypeptides having at least one of the biological properties of an EPH-like receptor (e.g. ligand binding, signal transduction). The isolated polypeptides will preferably have an amino acid sequence as shown in any of SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15 or SEQ ID NO: 17. Polypeptides of this invention may be full-length polypeptides having an extracellular domain, a transmembrane domain, and a cytoplasmic domain, or may be fragments thereof, e.g., those having only an extracellular domain or a portion thereof. It will be understood that the receptor polypeptides may also be analogs or naturally-occurring variants of the amino acid sequences shown in SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15 or SEQ ID NO: 17. Such analogs are generated by amino acid substitutions, deletions and/or insertions using methods available in the art.

Polypeptides of the invention are preferably the product of expression of an exogenous DNA sequences, i.e., EPH-like receptors are preferably produced by recombinant means. Methods of producing EPH-like receptors comprising culturing host cells which have been transformed or transfected with vectors expressing an EPH-like receptor are also encompassed. EPH-like receptors, particularly fragments, may also be produced by chemical synthesis. The polypeptides so produced may be glycosylated or nonglycosylated depending upon the host cell employed, or may have a methionine residue at the amino terminal end. The polypeptides so produced are identified and recovered from cell cultures employing methods which are conventional in the art.

EPH-like receptors of the present invention are used for the production of antibodies to the receptors. Antibodies to HEK receptors have been described in Example 4. Antibodies which recognize the polypeptides of the invention may be polyclonal or monoclonal and may be binding fragments or chimeric antibodies. Such antibodies are useful in the detection of EPH-like receptors in diagnostic assays in the purification of receptor, and in the modulation of EPH-like receptor activation.

As described in U.S. Pat. No. 5,716,934, the only known ligand for an EPH-like receptor is a protein which binds to and induces phosphorylation of the eck receptor. The ECK receptor ligand was previously identified as B61. (Holzman et al. Mol. Cell. Biol. 10, 5830-5838 (1990)). The availability of ECK receptor was important for the identification of a ligand since B61, although known, had not been previously implicated as an ECK receptor ligand. Therefore, EPH-like receptors having ligand binding domains are useful for the identification and purification of ligands. Polypeptides of the present invention may be used to identify and purify ligands for HEK5, HEK7, HEK8 and HEK11 receptors. Binding assays for the detection of potential ligands may be carried out in solution or by receptor immobilization on a solid support using methods such as those described in co-pending and co-owned U.S. Ser. No. 08/145,616. Such assays may employ an isolated ligand binding domain of a HEK receptor. Alternatively, a HEK ligand binding domain fused to an Ig domain may be used to detect the presence of HEK ligand on cell surfaces.

Soluble EPH-like receptors may be used to modulate (i.e., increase or decrease) the activation of the cell-associated receptors, typically by competing with the receptor for unbound ligand. Modulation of EPH-like receptor activation may in turn alter the proliferation and/or differentiation of receptor-bearing cells. For example, based upon the observed tissue distribution of the receptors of this invention (see Table 5), soluble HEK7 receptor is likely to primarily affect proliferation and/or differentiation of brain cells, while soluble HEK5 receptor may affect primarily brain and pancreatic cells, although effects of HEK5 receptor on other tissues may not be excluded.

Antibodies to EPH-like receptors are useful reagents for the detection of receptors in different cell types using immunoassays conventional to the art. Antibodies are also useful therapeutic agents for modulating receptor activation. Antibodies may bind to the receptor so as to directly or indirectly block ligand binding and thereby act as an antagonist of receptor activation. Alternatively, antibodies may act as an agonist by binding to receptor so as to faciliate ligand binding and bring about receptor activation at lower ligand concentrations. In addition, antibodies of the present invention may themselves act as a ligands by inducing receptor activation. It is also contemplated that antibodies to EPH-like receptors are useful for selection of cell populations enriched for EPH-like receptor bearing cells. Such populations may be useful in cellular therapy regimens where it is necessary to treat patients which are depleted for certain cell types.

The isolated nucleic acids of the present inventions may be used in hybridization assays for the detection and quantitation of DNA and/or RNA coding for HEK5, HEK7, HEK8, HEK11 and related receptors. Such assays are important in determining the potential of various cell types to express these receptors and in determining actual expression levels of HEK receptors. In addition, the nucleic acids are useful for detecting abnormalities in HEK receptor genes, such as translocations, rearrangements, duplications, etc.

Therapeutic regimens involving EPH-like receptors will typically involve use of the soluble form of the receptor contained in a pharmaceutical composition. Such pharmaecutical compositions may contain pharmaceutically acceptable carrier, diluents, fillers, salts, buffers, stabilizers and/or other materials well known in the art. Further examples of such constituents are described in Remington's Pharmaceutical Sciences 18th ed., A. R. Gennaro, ed. (1990). Administration of soluble EPH-like receptor compositions may be by a variety of routes depending upon the condition being treated, although typically administration will occur by intravenous or subcutaneous methods. Pharmaceutical compositions containing antibodies to EPH-like receptors will preferably include mouse-human chimeric antibodies or CDR-grafted antibodies in order to minimize the potential for an immune response by the patient to antibodies raised in mice. Other components of anti-EPH antibody compositions will be similar to those described for soluble receptor.

The amount of soluble Eph-like receptors or anti-Eph antibody in a pharmaceutical composition will depend upon the nature and severity of the condition being treated. Said amount may be determined for a given patient by one skilled in the art. It is contemplated that the pharmaceutical compositions of the present invention will contain about 0.01 μg to about 100 mg of soluble receptor or anti-Eph antibody per kg body weight.

A method for modulating the activation of an EPH-like receptor PTK is also provided by the invention. In practicing this method, a therapeutically effective amount of a soluble EPH-like receptor or an anti-EPH antibody is administered. The term "therapeutically effective amount" is that amount which effects an increase or decrease in the activation of an EPH-like receptor and will range from about 0.01 μto about 100 mg of soluble receptor or anti-EPH antibody per kg body weight. In general, therapy will be appropriate for a patient having a condition treatable by soluble receptor or anti-EPH antibody and it is contemplated that such a condition will in part be related to the state of proliferation and/or differentiation of receptor-bearing cells. Based upon the tissue distribution of HEK receptors shown in Table 4, treatment with the pharmaceutical compositions of the invention may be particularly indicated for disorders involving brain, heart, muscle, lung, or pancreas. However, some HEK receptors are displayed on a wide variety of tissues, so it is understood that the effects of modulating receptor activation may not be limited to those tissues described herein.

The following examples are offered to more fully illustrate the invention, but are not to be construed as limiting the scope thereof. Recombinant DNA methods used in the following examples are generally as described in Sambrook et al. Molecular Cloning: A Laboratory Manual Cold Spring Harbor Laboratory Press, 2nd ed. (1989)

EXAMPLE 1

Cloning and Sequencing of HEK Receptor cDNA

We have isolated clones for five members of the EPH sub-family of receptor PTKs from a human fetal brain cDNA library. Oligonucleotides were designed based on conserved amino acid sequences within the kinase domain. Primer I was based on the amino acid sequence Trp-Thr-Ala-Pro-Glu-Ala-Ile (SEQ ID NO: 1), which is well-conserved among PTKs of many families. Primer II was based on the sequence Val-Cys-Lys-Val-Ser-Asp-Phe-Gly (SEQ ID NO: 2), which is invariant among EPH sub-family members but, except for the sequence Asp-Phe-Gly, is rarely found in other PTKs. Fully degenerate oligonucleotides corresponding to reverse translations of these protein sequences were synthesized and utilized as primers in a polymerase chain reaction (PCR) with disrupted phage from a human fetal brain cDNA library as the template. The products of this PCR reaction were cloned into the plasmid vector pUC19 and the nucleotide sequence of the inserts was determined. Of the 35 PCR inserts sequenced, 27 were recognizable as portions of PTK genes. Their correspondence to previously published sequences is summarized in Table 1.

                                      TABLE 1                                      __________________________________________________________________________     Receptor                                                                              PCR Products                      Number of Clones                      __________________________________________________________________________     Elk    VCKVSDFGLSRYLQDDTSDPTYTSSLGGKIPVRWTAPEAI                                                                (SEQ ID NO: 3)                                                                          2                                        - HEK4, HEK7 VCKVSDFGLSRVLEDDPEAAYTT  RGGKIPIRWTAPEAI (SEQ ID NO: 4)                                                 5*                                       - HEK5 VCKVSDFGLSRFLEDDTSDPTYTSALGGKIPIRWTAPEAI (SEQ ID NO: 5) 8                                                       - HEK8 VCKVSDFGMSRVLEDDPEAAYTT                                                RGGKIPIRWTAPEAI (SEQ ID NO: 6)                                                4                                        - HEK11 VCKVSDFGLSRVIEDDPEAVYTTT  GGKIPVRWTAPEAI (SEQ ID NO: 7) 1                                                      - SRC VCKVSDFGLAR LIEDNEYTARQ                                                GAKFPIKWTAPEAI (SEQ ID NO: 8)                                                  6*                                       - PDGF-β VCKVSDFGLARDIMRDSNYISK  GSTFLPLKWTAPEAI (SEQ ID NO: 9)        __________________________________________________________________________                                              1                                      An asterisk indicates that different nucleic acid sequences encoded the        amino acid sequences shown.                                              

Six PCR inserts predict amino acid sequences which are identical to a portion of SRC, although they comprise two distinct nucleotide sequences. One insert appears to code for the human platelet derived growth factor (PDGF)-β receptor. The remaining 18 PCR inserts consist of 6 distinct nucleotide sequences, all of which appear to be fragments of EPH sub-family members. One of the sequence predicts an amino acid sequence identical to the corresponding region of rat Elk (Lhotak et al., 1991)) and is likely to represent its human homolog. Two inserts predict amino acid sequences which match the translation of the PCR fragment tyro-4 (Lai and Lemke, 1991)) but are clearly distinct at the nucleotide level while two others correspond to tyro-1 and tyro-5. The sixth PCR insert has a previously unreported EPH-related sequence. Since five of the clones contained portions of potential EPH sub-family members for which full-length sequences had not been reported, each was radiolabeled and used as a probe to screen a human fetal brain cDNA library. Several clones corresponding to each of the five probes were isolated. For each of the five receptors, the nucleotide sequence of the clone containing the largest portion of the predicted coding region was determined.

A single cDNA clone containing the complete coding region was isolated only for HEK4. The portions of HEK5, HEK7, HEK10 and HEK11 coding for the amino terminus of these receptors were not found in any of the clones. In order to obtain the complete coding sequence, the Rapid Amplification of cDNA Ends (RACE) technique was employed. In some cases, more than one round of RACE was necessary to obtain the missing portion of the coding region. Using this strategy, complete coding sequences were obtained for all clones except HEK7 which lacked the complete leader sequence. The DNA sequences of HEK5, HEK7, HEK8 and HEK11 are shown in FIGS. 1-4, respectively, and in SEQ ID NO: 10 (HEK5), SEQ ID NO: 12 (HEK7), SEQ ID NO: 14 (HEK 8) and SEQ ID NO: 16 (HEK11). The amino acid sequences are shown in SEQ ID NO: 11 (HEK5), SEQ ID NO: 13 (HEK7), SEQ ID NO: 15 (HEK8) and SEQ ID NO: 17 (HEK 11).

EXAMPLE 2

Analysis of HEK Receptor Sequences

HEK5, HEK7, HEK8 and HEK11 represent novel human EPH sub-family members, although homologs for all except HEK11 have been isolated from other species. We refer to human EPH receptor sub-family members as HEKs (human EPH-like kinases) following the nomenclature of Wicks et al., 1992). We have chosen names and numbers for these receptors to correspond with previously discovered members of the family in chicken (Ceks) and in mouse (Mek) (Sajjadi et al. 1991; Sajjadi and Pasquale, 1993; Pasquale, 1991). Extending the convention of designating the species of origin by the first letter, we refer to the rat homologs of the HEK receptors as Reks (rat EPH-like kinases).

HEK4 is the human homolog of the chicken receptor Cek4 (91% amino acid identity in the catalytic domain) and the mouse receptor Mek4 (96% amino acid identity in the catalytic domain). The amino acid sequence of HEK5 is very closely related (96% amino acid identity in the catalytic domain) to the chicken receptor Cek5 (Pasquale et al. J. Neuroscience 12, 3956-3967 (1992); Pasquale, 1991). HEK7 is probably the human homolog of the recently reported Cek7 (Sajjadi and Pasquale, 1993). HEK8 is likewise very closely related to Sek (Gilardi-Hebenstreit et al., 1992)) and Cek8 (95% amino acid identity in the catalytic domain) (Sajjadi and Pasquale, 1993)). The human homologs for Cek6 and Cek9 have yet to be reported, while the human homolog of Cek10 has just recently been published. One of our human receptors has no close relatives in other species and apparently represents a novel member of the EPH sub-family. We have designated this receptor HEK11, assuming that human homologs for Cek 9 and 10 will be named HEK9 and HEK10, respectively. A summary of known EPH sub-family members is shown in Table 2.

                  TABLE 2                                                          ______________________________________                                         EPH receptor sub-family members                                                      Human            Non-human homologs                                      ______________________________________                                         EPH                None identified                                               ECK None identified                                                            None identified#  Eek                                                          HEK4* Cek4, Mek4                                                               HEK5 Cek5, Nuk, ERK                                                            None identified# Cek6, Elk                                                     HEK7 Cek7, Ehkl                                                                HEK8 Cek8, Sek                                                                 None identified# Cek9                                                          HEK2 Cek10                                                                     HEK11 None identified                                                          None identified Ehk2                                                         ______________________________________                                          *published by Wicks et.al., 1992 as HEK                                        #Using the present nomenclature, the predicted human homolog of Eek is         designated HEK3. For Cek6, the predicted human homolog is designated HEK6      For Cek9, the predicted human homolog is designated HEK9.                

The predicted amino acid sequences of the four novel receptor clones and the previously known EPH sub-family members ECK (SEQ ID NO: 18), EPH (SEQ ID NO: 19), HEK2 (SEQ ID NO: 20) and HEK4 (SEQ ID NO: 21) were aligned as shown in FIG. 5. The four clones are closely related to each other and to the known EPH sub-family members. The extracellular domain sequences of all four novel receptors contain the Ig-loop, fibronectin-type III repeats, and cysteine-rich region characteristic of EPH sub-family members. The positions of the 20 cysteine residues are conserved among all sub-family members. Also completely conserved is the portion of the catalytic domain used as the basis for the EPH sub-family specific primer (Val-Cys-Lys-Val-Ser-Asp-Phe-Gly, SEQ ID NO: 2, amino acids 757-764 in FIG. 5). Table 3 summarizes the percentage of sequence identity between pairs of human EPH sub-family members. The lower portion of the table shows percent amino acid identity in the catalytic domain while the upper half shows percent amino acid identity in the extracellular region. The amino acid sequences of the EPH-like receptors are extremely well-conserved (60-89% amino acid identity) in the catalytic region but not as highly conserved in the extracellular region (38-65% amino acid identity), as would be expected for members of the same receptor sub-family.

                                      TABLE 3                                      __________________________________________________________________________     Eph family amino acid sequence comparison                                                          extracellular domains                                      EPH     ECK HEK4                                                                               HEK5                                                                               HEK7                                                                               HEK8                                                                               HEK2                                                                               HEK11                                          __________________________________________________________________________     EFH *   47  42  38  40  43  40  42                                               ECK 62 * 47 41 45 46 41 46                                                     HEK4 62 76 * 53 65 61 51 59                                                    HEK5 60 74 81 * 52 53 63 51                                                    HEK7 61 76 89 83 * 62 48 61                                                    HEK8 62 76 86 85 88 * 52 57                                                    HEK2 61 74 81 89 82 83 * 48                                                    HEK11 60 74 83 83 85 85 80 *                                                 Catalytic domains                                                              __________________________________________________________________________      Numbers shown are precent identity                                       

Pairwise comparisons of amino acid sequences can be used to construct phylogenetic trees depicting the evolutionary relatedness of a family of molecules. FIG. 6 is such a tree, which summarizes the relationships among the EPH sub-family members. Only one family member is shown from each group of cross-species homologs and the human representative was used whenever possible (refer to Table 2 for a summary of cross-species homologs). The branch lengths represent the degree of divergence between members. It has been shown previously that the EPH sub-family lies on a branch evolutionarily closer to the cytoplasmic PTKs than to other receptor PTKs (Lindberg and Hunter, 1993). Interestingly, the further one moves up the tree, the more closely related the receptors become and expression becomes more localized to the brain.

EXAMPLE 3

Construction and Expression of HEK Receptor Extracellular Domains

Soluble extracellular forms of HEK receptor proteins were constructed by deletion of DNA sequences encoding transmembrane and cytoplasmic domains of the receptors and introduction of a translation stop codon at the 3' end of the extracellular domain. A construct of the HEK5 extracellular domain had a stop codon introduced after lysine at position 524 as shown in FIG. 1; the HEK7 extracellular domain was constructed with a stop codon after glutamine at position 547 as shown in FIG. 2; the HEK 8 extracellular domain was constructed with a stop codon after threonine at position 547 as shown in FIG. 3.

HEK extracellular domain was amplified from a human fetal brain cDNA library by PCR using primers 5' and 3' to the extracellular domain coding region.

For HEK5, the primers

5' CTGCTCGCCGCCGTGGAAGAAACG (SEQ ID NO: 22) and;

5' GCGTCTAGATTATCACTTCTCCTGGATGCTTGTCTGGTA (SEQ ID NO: 23)

were used to amplify the extracellular domain and to provide a restriction site for cloning into plasmid pDSRα. In addition, the following primers were used to provide a translational start site, the elk receptor signal peptide for expression; and a restriction site for cloning into pDSRα:

5' GCGGTCGACGCCGCCGCCATGGCCCTGGATTGCCTGCTGCTGTTCCTCCTG (SEQ ID NO: 24) and;

5' CGTTTCTTCCACGGCGGCGAGCAGAGATGCCAGGAGGAACAGCAGCAGGCA ATC (SEQ ID NO: 25)

The resulting construct resulted in fusion of DNA encoding the elk signal sequence Met-Ala-Leu-Asp-Cys-Leu-Leu-Leu-Phe-Leu-Leu-Ala-Ser (SEQ ID NO: 26) to the first codon of the HEK5 receptor.

The resulting HEK5 extracellular domain was cloned into pDSRα after digestion with SalI and XbaI and transfected into CHO cells for expression.

HEK8 extracellular domain was amplified from a human fetal brain cDNA library by PCR using primers 5' and 3' to the extracellular domain coding region. For HEK8, the primers

5' GAATTCGTCGACCCGGCGAACCATGGCTGGGAT (SEQ ID NO: 31) and

5' GAATTCTCTAGATTATCATGTGGAGTTAGCCCCATCTC (SEQ ID NO: 32)

were used to amplify the extracellular domain and to provide restriction sites for cloning into plasmid pDSRα.

The resulting HEK8 extracellular domain was cloned into pDSRα after digestion with SalI and XbaI and transferred CHO cells for expression.

HEK7 extracellular domain was amplified from a human fetal brain cDNA library by PCR using primers 5' and 3' to the extracellular domain coding region. For HEK7, the primers

5' TTCGCCCTATTTTCGTGTCTCTTCGGGATTTGCGACGCTCTCCGGACCCTCCTG GCCAGC (SEQ ID NO: 33) and

5' GAATTCTCTAGATTATCACTGGCTTTGATCGCTGGAT (SEQ ID NO: 34)

were used to amplify the extracellular domain. In addition, the following primers were used to provide a translational start site, the HEK8 receptor signal peptide sequence, and restriction site for cloning into plasmid pDSRα.

5' GAATTCGTCGACCCGGCGAACCATGGCTGGGATTTTCTATTTCGCCCTATTTTCGT GTCT (SEQ ID NO: 35)

5' GAATTCTCTAGATTATCACTGGCTTTGATCGCTGGAT (SEQ ID NO: 36)

The resulting construct resulted in fusion of DNA incoding HEK8 signal sequence Met-Ala-Gly-Ile-Phe-Tyr-Phe-Ala-Leu-Phe-Ser-Cys-Leu-Phe-Gly-Ile-Cys-Asp (SEQ ID NO: 37) to the first codon of the HEK7 receptor.

The resulting HEK7 extracellular domain was cloned into pDSRα after digestion with SalI and XbaI and transfected into CHO cells for expression.

EXAMPLE 4

Antibodies to HEK Receptors

Antibodies to HEK receptor proteins were generated which recognize the extracellular domain by using bacterial fusion proteins as the antigen. Antibodies were also generated which recognize the cytoplasmic domain by using synthetic peptides as the antigen.

The methodology employed has been previously described (Harlow and Lane, In Antibodies: A Laboratory Manual, 1988). For the extracellular domain antibodies, cDNAs were inserted into the pATH vector (see Table 4 for the regions of each receptor encoded by this construct). These constructs were expressed in bacteria and the resultant TrpE-fusion proteins were purified by SDS-polyacrylamide gel electrophoresis. For the cytoplasmic domain anti-peptide antibodies, peptides were synthesized (see Table 4 for the sequences) and covalently coupled to keyhole limpet hemocyanin . The fusion proteins and coupled peptides were used as antigens in rabbits and antisera were generated and characterized as described (Harlow and Lane, 1988). Anti-peptide antibodies were affinity purified by using a SulfoLink kit (Pierce, Rockford Ill.).

                  TABLE 4                                                          ______________________________________                                         HEK Receptor Antigens                                                                                            Amino Acids                                      in Fusion                                                                    Receptor Peptide Sequences Protein                                           ______________________________________                                         HEK4   CLETQSKNGPVPV (SEQ ID NO:38)                                                                              22-159                                       HEK5 CRAQMNQIQSVEV (SEQ ID NO:39) 31-168                                          - HEK7 CMKVQLVNGMVPL (SEQ ID NO:40) 335-545                                    - HEK8 CMRTQMQQMHGRMVPV (SEQ ID NO:41) 27-188                                  - HEK11 CQMLHLHGTGIQV (SEQ ID NO:42) 187-503                                ______________________________________                                    

EXAMPLE 5

HEK/TrkB Chimeric Receptors

1. Generation of pSJA1 encoding rat trkB cytoplasmic domain.

All of the chimeric receptors are composed of the extracellular domain and the transmembrane region of one of the HEK receptors and the intracellular portion of rat trkB. To simplify each individual construction, an intermediate or parental plasmid, called RtrkB/AflII (or pSJA1), was generated. First, without altering the coded peptide sequence, an AflII site (CTTAAG) was introduced into position 2021 (cytosine at position 2021 (C2021) to guanine at position 2026 (G2026, CTCAAG) of the rat trkB cDNA (Middlemas, et al., Mol. Cell. Biol. 11, 143-153 (1991)) by PCR aided mutagenesis. Briefly, PCR primers were synthesized based on the rat trkB cDNA sequence. Primer I encompassed C2003 to G2034 of the cDNA. This primer contained two mutations, a cytosine to thymine(T) substitution at position 2023 (C2023T) and an insertion of an adenine(A) in between T2013 and G2014. These mutations created the AflII site at position C2021 and an additional XhoI site flanking the AflII site. Primer II was in the reverse direction encompassing T2141 to A2165 of the cDNA which bore an ApaI site. The PCR fragment produced with these primers and the rat trkB cDNA template was digested with XhoI and ApaI enzymes and sub cloned into the XhoI and ApaI sites of an expression vector, pcDNA3 (InVitroGen), to generate pSJA1-b. Following, pSJA1-b was linearized with ApaI and ligated with a BanII digested rat trkB cDNA fragment (G2151 to G4697) to reconstitute a larger fragment (C2021 to G4697) including the coding sequence of the whole intracellular domain of the rat trkB protein (L442 to G790) and 1571 residues (A3131 to G4697) of the 1627 nucleotide 3'-end non-coding region of the cDNA.

2. Generation of HEK8/rat trkB (pSJA5) chimera.

HEK8/rat trkB chimera was generated with a similar strategy as mentioned above. A SalI/BsaI cDNA fragment was first isolated from plasmid TK10/FL13. This fragment included the nucleotide sequence from the beginning to T1689 of the HEK8 cDNA (FIG. 3). Then, a pair of oligonucleotides was synthesized based on the HEK8 cDNA sequence. The sequence of the first oligonucleotide was the same as G1690 to C1740 of the Hek8 cDNA, with an additional C residue added to its 3'-end. The second oligonucleotide was in the reverse orientation of the HEK8 cDNA. It contained C1694 to C1740 of the HEK8 cDNA sequence and an additional five residue motif, TTAAG, at its 5'-end. These two oligonucleotides were kinased and annealed with equal molar ratio, to create a double strand DNA fragment with the sequence of G1690 to C1740 of the HEK8 cDNA and with the BsaI and the AflII cohesive ends at its 5' and 3' ends, respectively. This fragment was ligated together with the SalI/BsaI cDNA fragment into XhoI/AflII linearized pSJA1 to generate the HEK8/RtrkB (pSJA5) chimerical construct.

3. Generation of HEK11/rat trkB (pSJA6) chimera.

To generate the HEK11/rat trkB chimera, a SalI/AccI fragment covering the sequence of nucleotide C1 to T1674 of the HEK11 cDNA (FIG. 4) was first isolated from plasmid TK19T3. Then, a pair of oligonucleotides was synthesized based on the HEK11 cDNA sequence. The first oligonucleotide had the same sequence as from nucleotide A1666 to T1691 of the HEK11 cDNA, which contained the AccI site. The second oligonucleotide was in the reverse orientation of the HEK11 cDNA. It encompassed G1895 to T1919 of the HEK11 cDNA sequence. An additional ten residue motif, CCCGCTTAAG (SEQ ID NO: 43), was added to the 5'-end of this oligonucleotide to introduce an AflII site, which would be used to link the external domain and the transmembrane region of the HEK11 receptor to the intracellular domain of the rat trkB cDNA cloned in pSJA1 in the same reading frame. PCR was performed with these oligonucleotides as primers and the HEK11 cDNA as template. The PCR fragment was digested with AccI and AflII enzymes and ligated with the SalI/AccI cDNA fragment and the XhoI/AflII linearized pSJA1 to generate the HEK11/rat trkB (pSJA6) chimerical construct.

EXAMPLE 6

Tissue Distribution of HEK Receptors

The distribution of mRNA expression for HEK4, HEK5, HEK7, HEK8 and HEK11 receptors in human and rat tissues was examined by Northern blot hybridization.

Rat total RNA was prepared from tissues using the method of Chomczynski and Sacchi (Anal. Biochem 162, 156-159 (1987)). The RNA was separated by formaldehyde-agarose electrophoresis and transferred to Hybond-N membranes (Amersham, Arlington Heights, Ill.) using 20× SSC (Maniatis et al. 1982). The membrane was dried at 80° C. in vacuo for 30 minutes, then crosslinked for 3 minutes on a UV transilluminator (Fotodyne, New Berlin, Wis.). The membrane was prehybridized for 2 hours at 42° C. in 50% formamide, 5× SSPE, 5× Denhardt's , 0.2% SDS, and 100 μg/ml denatured herring sperm DNA (Maniatis et al. 1982). Northern blots of human tissue were purchased from Clontech (Palo Alto, Calif.). Probes were prepared by labeling the fragment of cDNA which encoded the extracellular domain of the receptor with ³² P-dCTP using a hexanucleotide random priming kit (Boehringer Mannheim, Indianapolis, Ind.) to a specific activity of at least 1×10⁹ cpm/ug. The probe was hybridized to the membrane at a concentration of 1-5 ng/ml at 42° C. for 24 to 36 hours in a buffer similar to the prehybridization buffer except that 1× Denhardt's was used. After hybridization, the membranes were washed 2 times for 5 minutes each in 2×0 SSC, 0.1% SDS at room temperature followed by two 15 minute washes in 0.5× SSC, 0.1% SDS at 55° C. Blots were exposed for 1-2 weeks using Kodak XAR film (Kodak, Rochester, N.Y.) with a Dupont Lightning Plus intensifying screen. The results are shown in FIGS. 7-11.

Homologs for HEK4 have been previously identified from mouse, chicken, and rat. In the adult mouse, expression is detected primarily in the brain and testis (Sajjadi et al. 1991). A slightly different pattern was found in adult chicken tissues, with the main sources of expression being the brain, liver, and kidney. Lower levels of expression were detectable in the lung and heart (Marcelle & Eichmann, Oncogene 7, 2479-2487 (1992)). A fragment of the Rek4 gene (tyro-4) has been isolated and used to look at tissue expression in the adult rat (Sajjadi et al. 1991). The brain was the only tissue that expressed Rek4 mRNA. However, RNA from lung or testis were not examined. Previous studies on HEK4 only looked at the expression of the mRNA in cell lines, where it was found in one pre-B cell line and two T-cell lines (Wicks et al. 1992). The significance of this with regard to in vivo expression remains to be determined. In this study we have looked at the HEK4 expression in human tissues, and also the expression of Rek4 in rat tissues. The HEK4 mRNA corresponds to a single transcript with a size of about 7 kb (FIG. 7A). HEK4 mRNA was most abundantly expressed in placenta, with lower levels present in heart, brain, lung, and liver. On prolonged exposures, trace amounts of mRNA were detectable in kidney and pancreas. Expression in the rat was more similar to that detected in the mouse and chicken. Rek4 was expressed at the lowest levels of any of the family members characterized herein. A transcript of about 7 kb was detectable in rat lung, with a lower amount detectable in brain (FIG. 7B). Also, a 4 kb transcript was expressed in rat testis. Because the transcripts were barely detectable using total RNA, some of the other rat tissues may contain amounts of Rek4 below the level of detection.

The expression of HEK5 in adult tissues has been previously studied in chicken and rat. Studies in the chicken have identified the Cek5 protein in the brain and liver, with a smaller protein detected in the intestine. In the rat, the tyro-5 fragment detected mRNA expression only in the adult brain, though intestine was not examined (Lai and Lemke, 1991). Our results show that HEK5 mRNA was expressed at much higher levels than HEK4 and was found as transcripts of several sizes. The most abundant mRNAs were of approximately 4.0 and 4.4 kb, with lesser amounts of higher molecular weight transcripts of 9.5 kb and longer (FIG. 8A). The HEK5 mRNA was most abundantly expressed in placenta, but was also highly expressed in brain, pancreas, kidney, muscle, and lung. Longer exposures of the blots revealed the presence of transcripts in heart and liver as well. The rat homolog of HEK5 (Rek5) showed a somewhat similar pattern of expression. Rek5 was most abundant in intestine, followed by brain, kidney, lung, thymus, stomach, and ovary (FIG. 8B). Expression was not detectable in testis, muscle, heart, or liver. During our analysis of this family, we concluded that the rat Erk fragment (Chan & Watt, 1991) likely encodes a portion of the Rek5 receptor. Erk expression was examined in several rat tissues and found only in the lung. The reason for the discrepancy between that report and what we and others (Lai & Lemke, 1991) have found is unclear.

Homologs for HEK8 have been identified from chicken, mouse, and rat. In the adult chicken, a single Cek8 transcript was found to be expressed at high levels in the brain, with expression also detected in the kidney, lung, muscle, and thymus. The expression of the mouse homolog of HEK8, Sek, has been detected as a single transcript with abundant expression in the adult brain and lower expression in the heart, lung and kidney. A fragment of Rek8 (tyro-1) was used to look at expression in rat tissues, with expression found only in the brain (Lai & Lemke, 1991). We found that HEK8 mRNA was expressed at levels comparable to that of HEK5. Multiple transcripts were also observed, the most abundant at 7 kb and 5 kb. The highest level of mRNA expression was seen in the brain, although substantial levels were detected in other tissues including heart, lung, muscle, kidney, placenta, and pancreas. Expression in liver was much lower than in the other tissues. The only difference in expression patterns between human and mouse was expression in human muscle, also seen for Cek8 in chicken. Among the rat tissues, Rek8 was most highly expressed in the brain, followed by the lung, heart, and testis (FIG. 10B). In contrast to HEK8, expression of Rek8 appeared to be lower in muscle and kidney, two tissues where HEK8 was readily detectable. In addition, Rek8 was not expressed as a 5.0 kb transcript, as it was not visible even on prolonged exposures.

During the analysis of this family, we deduced that HEK7 is the human homolog of Cek7. The only expression seen in adult chicken was an 8.5 kb transcript found in the brain (Sajjadi & Pasquale, 1993). Of the five EPH sub-family members described here, HEK7 was the most restricted in its expression pattern. Analysis of human mRNA revealed significant expression only in the brain, with a much lower level detectable in the placenta (FIG. 9A). Prolonged exposures did not reveal expression in any other tissue examined. Two prominent transcripts were found in brain, the most highly expressed with a size of 6 kb and the other with a length of 9 kb. In the placenta, however, only the 9 kb transcript was detected. Rek7 mRNA was expressed in a pattern similar to HEK7. The highest level of expression was found in brain, with a much lower level in ovary (FIG. 9B). The transcripts were of similar size as for HEK7, with the 6 kb transcript detected only in brain.

HEK11 was expressed as several transcripts, with major mRNAs of length 7.5, 6.0 and 3.0 kb and minor transcripts of 4.4 and 2.4 kb (FIG. 11A). All five mRNAs were expressed at the highest levels in brain, followed by heart. Placenta, lung and kidney had significant amounts of four of the five transcripts, with lower expression seen in muscle. Pancreas had barely detectable amounts of HEK11 mRNA, while liver had no detectable HEK11 transcript. Rek11 had a similar pattern of expression, with four transcripts (10, 7.5, 3.5 and 3.0 kb) detected in brain (FIG. 11B).

The relative level of mRNA expression for each of the five receptors in all tissues studied is summarized in Table 5.

                  TABLE 5                                                          ______________________________________                                         Tissue Distribution of HEK Receptors                                                   HEK4     HEK5     HEK7   HEK8   HEK11                                  ______________________________________                                         Human                                                                            Brain ++  ++ ++ +++ ++                                                         Heart + + bd ++ +                                                              Kidney + + bd + +                                                              Liver + + bd + bd                                                              Lung + + bd ++ +                                                               Muscle + + bd ++ +                                                             Pancreas + ++ bd + bd                                                          Placenta +++ +++ bd ++ +                                                     ______________________________________                                           Rat                                                                            Brain + ++ +++ +++ ++                                                          Heart bd bd bd + bd                                                            Intestine bd +++ bd bd bd                                                      Kidney bd ++ bd bd bd                                                          Liver bd bd bd bd bd                                                           Lung + + bd ++ bd                                                              Muscle bd bd bd bd bd                                                          Ovary bd + + bd bd                                                             Stomach bd + bd bd bd                                                          Testis + bd bd + bd                                                            Thymus bd + bd bd bd                                                         ______________________________________                                          bd = below detection                                                     

The transcripts for HEKs 4,5,8, and 11 were rather widely distributed in human tissue while HEK7 was specific for brain. Expression patterns between rat and human tissue were roughly comparable given that the rat blots were less sensitive due to the use of total RNA rather than polyA⁺. As was found for the Cek mRNAs by Sajjadi and Pasquale (Sajjadi & Pasquale, 1993), often there were several different size transcripts detected for a single receptor. The size distribution of the transcripts appears to be both tissue and species specific. Previous work has shown that the smaller transcript of Mek4 encodes a potentially secreted receptor (Sajjadi et al. 1991).

The following sections describe Materials and Methods used to carry out experiments described in Example 1.

Isolation, Cloning and Sequencing of HEK Receptor cDNAs

Fragments containing a portion of the catalytic domain of EPH sub-family receptors were generated using a polymerase chain reaction (PCR) with disrupted phage from a human fetal brain cDNA library as a template. A 10 μl aliquot of the cDNA library (Stratagene, La Jolla, Calif.) was treated at 70° C. for 5 minutes to disrupt the phage particles, then cooled on wet ice. The disrupted phage were added to 10 μl of 10× Taq polymerase buffer, 8 ul of 2 mM each DNTP, 100 picomoles of each primer, and 1.5 μl of Taq polymerase (Promega, Madison, Wis.) in a total volume of 100 μl . The reaction was run for 35 cycles, each consisting of 1 minute at 96° C., 1 minute at 50° C., and 2 minutes at 72° C. A 5 minute, 72° C. incubation was added at the end to ensure complete extension. The primers used were degenerate mixtures of oligonucleotides based on amino acid sequences which are highly conserved among EPH sub-family members.

5' AGGGAATTCCAYCGNGAYYTNGCNGC' (SEQ ID NO: 27);

5' AGGGGATCCRWARSWCCANACRTC' (SEQ ID NO: 28).

The products of the PCR reaction were digested with EcoRI and BamHI and cloned into M13mp19 (Messing, Methods Enzymol. (1983)) for sequence analysis. The five clones which were identified as fragments of EPH receptor sub-family members were labeled with ³² P-dCTP by random priming and each was used to screen Genescreen nitrocellulose filters (NEN, Boston, Mass.) containing plaques from the human fetal brain cDNA library. Phage stocks prepared from positively screening plaques were plated and rescreened with the same probe in order to obtain single clones. cDNA inserts were transferred into pBluescript using the in vivo excision protocol supplied with the cDNA library (Stratagene, La Jolla, Calif.). Nucleotide sequences were determined using Taq DyeDeoxy Terminator Cycle Sequencing kits and an Applied Biosystems 373A automated DNA sequencer (Applied Biosystems, Foster City, Calif.).

5' Race

The 5' ends of the cDNAs were isolated using a 5' RACE kit (GIBCO/BRL, Gaithersburg, Md.) following the manufacturer's instructions. Excess primers were removed after first strand cDNA synthesis using ultrafree-MC cellulose filters (30,000 molecular weight cutoff, Millipore, Bedford, Mass.). Amplified PCR products were digested with the appropriate restriction enzymes, separated by agarose gel electrophoresis, and purified using a Geneclean kit (Bio101, La Jolla, Calif.). The purified PCR product was ligated into the plasmid vector pUC19 (Yanisch-Perron et al. Gene 33, 103-119 (1985)) which had been digested with appropriate restriction enzymes and the ligation mixture was introduced into host bacteria by electroporation. Plasmid DNA was prepared from the resulting colonies. Those clones with the largest inserts were selected for DNA sequencing.

While the present invention has been described in terms of preferred embodiments, it is understood that variations and modifications will occur to those skilled in the art. Therefore, it is intended that the appended claims cover all such equivalent variations which come within the scope of the invention as claimed.

    __________________________________________________________________________     #             SEQUENCE LISTING                                                    - -  - - (1) GENERAL INFORMATION:                                              - -    (iii) NUMBER OF SEQUENCES: 43                                           - -  - - (2) INFORMATION FOR SEQ ID NO:1:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 7 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:1:                         - -      Trp Thr Ala Pro Glu Ala Ile                                               1             - #  5                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:2:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 8 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:2:                         - -      Val Cys Lys Val Ser Asp Phe Gly                                           1             - #  5                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:3:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 40 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:3:                         - -      Val Cys Lys Val Ser Asp Phe Gly - # Leu Ser Arg Tyr Leu Gln        Asp Asp                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Thr Ser Asp Pro Thr Tyr Thr Ser - # Ser Leu Gly Gly Lys Ile        Pro Val                                                                                           20 - #                 25 - #                 30              - -      Arg Trp Thr Ala Pro Glu Ala Ile                                                   35     - #             40                                          - -  - - (2) INFORMATION FOR SEQ ID NO:4:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 38 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:4:                         - -      Val Cys Lys Val Ser Asp Phe Gly - # Leu Ser Arg Val Leu Glu         Asp Asp                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Pro Glu Ala Ala Tyr Thr Thr Arg - # Gly Gly Lys Ile Pro Ile        Arg Trp                                                                                           20 - #                 25 - #                 30              - -      Thr Ala Pro Glu Ala Ile                                                           35                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:5:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 40 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:5:                         - -      Val Cys Lys Val Ser Asp Phe Gly - # Leu Ser Arg Phe Leu Glu         Asp Asp                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Thr Ser Asp Pro Thr Tyr Thr Ser - # Ala Leu Gly Gly Lys Ile        Pro Ile                                                                                           20 - #                 25 - #                 30              - -      Arg Trp Thr Ala Pro Glu Ala Ile                                                   35     - #             40                                          - -  - - (2) INFORMATION FOR SEQ ID NO:6:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 38 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:6:                         - -      Val Cys Lys Val Ser Asp Phe Gly - # Met Ser Arg Val Leu Glu         Asp Asp                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Pro Glu Ala Ala Tyr Thr Thr Arg - # Gly Gly Lys Ile Pro Ile        Arg Trp                                                                                           20 - #                 25 - #                 30              - -      Thr Ala Pro Glu Ala Ile                                                           35                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:7:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 38 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:7:                         - -      Val Cys Lys Val Ser Asp Phe Gly - # Leu Ser Arg Val Ile Glu         Asp Asp                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Pro Glu Ala Val Tyr Thr Thr Thr - # Gly Gly Lys Ile Pro Val        Arg Trp                                                                                           20 - #                 25 - #                 30              - -      Thr Ala Pro Glu Ala Ile                                                           35                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:8:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:8:                         - -      Val Cys Lys Val Ser Asp Phe Gly - # Leu Ala Arg Leu Ile Glu         Asp Asn                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Glu Tyr Thr Ala Arg Gln Gly Ala - # Lys Phe Pro Ile Lys Trp        Thr Ala                                                                                           20 - #                 25 - #                 30              - -      Pro Glu Ala Ile                                                                   35                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:9:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 37 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:9:                         - -      Val Cys Lys Val Ser Asp Phe Gly - # Leu Ala Arg Asp Ile Met         Arg Asp                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Ser Asn Tyr Ile Ser Lys Gly Ser - # Thr Phe Leu Pro Leu Lys        Trp Thr                                                                                           20 - #                 25 - #                 30              - -      Ala Pro Glu Ala Ile                                                               35                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:10:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 2962 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: 1..2913                                                 - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:10:                        - - CTG CTC GCC GCC GTG GAA GAA ACG CTA ATG GA - #C TCC ACT ACA GCG ACT            48                                                                        Leu Leu Ala Ala Val Glu Glu Thr Leu Met As - #p Ser Thr Thr Ala Thr              1               5 - #                 10 - #                 15               - - GCT GAG CTG GGC TGG ATG GTG CAT CCT CCA TC - #A GGG TGG GAA GAG GTG            96                                                                        Ala Glu Leu Gly Trp Met Val His Pro Pro Se - #r Gly Trp Glu Glu Val                         20     - #             25     - #             30                   - - AGT GGC TAC GAT GAG AAC ATG AAC ACG ATC CG - #C ACG TAC CAG GTG TGC           144                                                                        Ser Gly Tyr Asp Glu Asn Met Asn Thr Ile Ar - #g Thr Tyr Gln Val Cys                     35         - #         40         - #         45                       - - AAC GTG TTT GAG TCA AGC CAG AAC AAC TGG CT - #A CGG ACC AAG TTT ATC           192                                                                        Asn Val Phe Glu Ser Ser Gln Asn Asn Trp Le - #u Arg Thr Lys Phe Ile                 50             - #     55             - #     60                           - - CGG CGC CGT GGG GCC CAC CGC ATC CAC GTG GA - #G ATG AAG TTT TCG GTG           240                                                                        Arg Arg Arg Gly Ala His Arg Ile His Val Gl - #u Met Lys Phe Ser Val             65                 - # 70                 - # 75                 - # 80        - - CGT GAC TGC AGC AGC ATC CCC AGC GTG CCT GG - #C TCC TGC AAG GAG ACC           288                                                                        Arg Asp Cys Ser Ser Ile Pro Ser Val Pro Gl - #y Ser Cys Lys Glu Thr                             85 - #                 90 - #                 95               - - TTC AAC CTC TAT TAC TAT GAG GCT GAC TTT GA - #C TCG GCC ACC AAG ACC           336                                                                        Phe Asn Leu Tyr Tyr Tyr Glu Ala Asp Phe As - #p Ser Ala Thr Lys Thr                        100      - #           105      - #           110                   - - TTC CCC AAC TGG ATG GAG AAT CCA TGG GTG AA - #G GTG GAT ACC ATT GCA           384                                                                        Phe Pro Asn Trp Met Glu Asn Pro Trp Val Ly - #s Val Asp Thr Ile Ala                    115          - #       120          - #       125                       - - GCC GAC GAG AGC TTC TCC CAG GTG GAC CTG GG - #T GGC CGC GTC ATG AAA           432                                                                        Ala Asp Glu Ser Phe Ser Gln Val Asp Leu Gl - #y Gly Arg Val Met Lys                130              - #   135              - #   140                           - - ATC AAC ACC GAG GTG CGG AGC TTC GGA CCT GT - #G TCC CGC AGC GGC TTC           480                                                                        Ile Asn Thr Glu Val Arg Ser Phe Gly Pro Va - #l Ser Arg Ser Gly Phe            145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - TAC CTG GCC TTC CAG GAC TAT GGC GGC TGC AT - #G TCC CTC ATC GCC         GTG      528                                                                     Tyr Leu Ala Phe Gln Asp Tyr Gly Gly Cys Me - #t Ser Leu Ile Ala Val                           165  - #               170  - #               175               - - CGT GTC TTC TAC CGC AAG TGC CCC CGC ATC AT - #C CAG AAT GGC GCC ATC           576                                                                        Arg Val Phe Tyr Arg Lys Cys Pro Arg Ile Il - #e Gln Asn Gly Ala Ile                        180      - #           185      - #           190                   - - TTC CAG GAA ACC CTG TCG GGG GCT GAG AGC AC - #A TCG CTG GTG GCT GCC           624                                                                        Phe Gln Glu Thr Leu Ser Gly Ala Glu Ser Th - #r Ser Leu Val Ala Ala                    195          - #       200          - #       205                       - - CGG GGC AGC TGC ATC GCC AAT GCG GAA GAG GT - #G GAT GTA CCC ATC AAG           672                                                                        Arg Gly Ser Cys Ile Ala Asn Ala Glu Glu Va - #l Asp Val Pro Ile Lys                210              - #   215              - #   220                           - - CTC TAC TGT AAC GGG GAC GGC GAG TGG CTG GT - #G CCC ATC GGG CGC TGC           720                                                                        Leu Tyr Cys Asn Gly Asp Gly Glu Trp Leu Va - #l Pro Ile Gly Arg Cys            225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - ATG TGC AAA GCA GGC TTC GAG GCC GTT GAG AA - #T GGC ACC GTC TGC         CGA      768                                                                     Met Cys Lys Ala Gly Phe Glu Ala Val Glu As - #n Gly Thr Val Cys Arg                           245  - #               250  - #               255               - - GGT TGT CCA TCT GGG ACT TTC AAG GCC AAC CA - #A GGG GAT GAG GCC TGT           816                                                                        Gly Cys Pro Ser Gly Thr Phe Lys Ala Asn Gl - #n Gly Asp Glu Ala Cys                        260      - #           265      - #           270                   - - ACC CAC TGT CCC ATC AAC AGC CGG ACC ACT TC - #T GAA GGG GCC ACC AAC           864                                                                        Thr His Cys Pro Ile Asn Ser Arg Thr Thr Se - #r Glu Gly Ala Thr Asn                    275          - #       280          - #       285                       - - TGT GTC TGC CGC AAT GGC TAC TAC AGA GCA GA - #C CTG GAC CCC CTG GAC           912                                                                        Cys Val Cys Arg Asn Gly Tyr Tyr Arg Ala As - #p Leu Asp Pro Leu Asp                290              - #   295              - #   300                           - - ATG CCC TGC ACA ACC ATC CCC TCC GCG CCC CA - #G GCT GTG ATT TCC AGT           960                                                                        Met Pro Cys Thr Thr Ile Pro Ser Ala Pro Gl - #n Ala Val Ile Ser Ser            305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - GTC AAT GAG ACC TCC CTC ATG CTG GAG TGG AC - #C CCT CCC CGC GAC         TCC     1008                                                                     Val Asn Glu Thr Ser Leu Met Leu Glu Trp Th - #r Pro Pro Arg Asp Ser                           325  - #               330  - #               335               - - GGA GGC CGA GAG GAC CTC GTC TAC AAC ATC AT - #C TGC AAG AGC TGT GGC          1056                                                                        Gly Gly Arg Glu Asp Leu Val Tyr Asn Ile Il - #e Cys Lys Ser Cys Gly                        340      - #           345      - #           350                   - - TCG GGC CGG GGT GCC TGC ACC CGC TGC GGG GA - #C AAT GTA CAG TAC GCA          1104                                                                        Ser Gly Arg Gly Ala Cys Thr Arg Cys Gly As - #p Asn Val Gln Tyr Ala                    355          - #       360          - #       365                       - - CCA CGC CAG CTA GGC CTG ACC GAG CCA CGC AT - #T TAC ATC AGT GAC CTG          1152                                                                        Pro Arg Gln Leu Gly Leu Thr Glu Pro Arg Il - #e Tyr Ile Ser Asp Leu                370              - #   375              - #   380                           - - CTG GCC CAC ACC CAG TAC ACC TTC GAG ATC CA - #G GCT GTG AAC GGC GTT          1200                                                                        Leu Ala His Thr Gln Tyr Thr Phe Glu Ile Gl - #n Ala Val Asn Gly Val            385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - ACT GAC CAG AGC CCC TTC TCG CCT CAG TTC GC - #C TCT GTG AAC ATC         ACC     1248                                                                     Thr Asp Gln Ser Pro Phe Ser Pro Gln Phe Al - #a Ser Val Asn Ile Thr                           405  - #               410  - #               415               - - ACC AAC CAG GCA GCT CCA TCG GCA GTG TCC AT - #C ATG CAT CAG GTG AGC          1296                                                                        Thr Asn Gln Ala Ala Pro Ser Ala Val Ser Il - #e Met His Gln Val Ser                        420      - #           425      - #           430                   - - CGC ACC GTG GAC AGC ATT ACC CTG TCG TGG TC - #C CAG CCG GAC CAG CCC          1344                                                                        Arg Thr Val Asp Ser Ile Thr Leu Ser Trp Se - #r Gln Pro Asp Gln Pro                    435          - #       440          - #       445                       - - AAT GGC GTG ATC CTG GAC TAT GAG CTG CAG TA - #C TAT GAG AAG GAG CTC          1392                                                                        Asn Gly Val Ile Leu Asp Tyr Glu Leu Gln Ty - #r Tyr Glu Lys Glu Leu                450              - #   455              - #   460                           - - AGT GAG TAC AAC GCC ACA GCC ATA AAA AGC CC - #C ACC AAC ACG GTC ACG          1440                                                                        Ser Glu Tyr Asn Ala Thr Ala Ile Lys Ser Pr - #o Thr Asn Thr Val Thr            465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - GGC CTC AAA GCC GGC GCC ATC TAT GTC TTC CA - #G GTG CGG GCA CGC         ACT     1488                                                                     Gly Leu Lys Ala Gly Ala Ile Tyr Val Phe Gl - #n Val Arg Ala Arg Thr                           485  - #               490  - #               495               - - GTG GCA GGC TAC GGG CGC TAC AGC GGC AAG AT - #G TAC TTC CAG ACC ATG          1536                                                                        Val Ala Gly Tyr Gly Arg Tyr Ser Gly Lys Me - #t Tyr Phe Gln Thr Met                        500      - #           505      - #           510                   - - ACA GAA GCC GAG TAC CAG ACA AGC ATC CAG GA - #G AAG TTG CCA CTC ATC          1584                                                                        Thr Glu Ala Glu Tyr Gln Thr Ser Ile Gln Gl - #u Lys Leu Pro Leu Ile                    515          - #       520          - #       525                       - - ATC GGC TCC TCG GCC GCT GGC CTG GTC TTC CT - #C ATT GCT GTG GTT GTC          1632                                                                        Ile Gly Ser Ser Ala Ala Gly Leu Val Phe Le - #u Ile Ala Val Val Val                530              - #   535              - #   540                           - - ATC GCC ATC GTG TGT AAC AGA CGG GGG TTT GA - #G CGT GCT GAC TCG GAG          1680                                                                        Ile Ala Ile Val Cys Asn Arg Arg Gly Phe Gl - #u Arg Ala Asp Ser Glu            545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - TAC ACG GAC AAG CTG CAA CAC TAC ACC AGT GG - #C CAC ATA ACC CCA         GGC     1728                                                                     Tyr Thr Asp Lys Leu Gln His Tyr Thr Ser Gl - #y His Ile Thr Pro Gly                           565  - #               570  - #               575               - - ATG AAG ATC TAC ATC GAT CCT TTC ACC TAC GA - #G GAC CCC AAC GAG GCA          1776                                                                        Met Lys Ile Tyr Ile Asp Pro Phe Thr Tyr Gl - #u Asp Pro Asn Glu Ala                        580      - #           585      - #           590                   - - GTG CGG GAG TTT GCC AAG GAA ATT GAC ATC TC - #C TGT GTC AAA ATT GAG          1824                                                                        Val Arg Glu Phe Ala Lys Glu Ile Asp Ile Se - #r Cys Val Lys Ile Glu                    595          - #       600          - #       605                       - - CAG GTG ATC GGA GCA GGG GAG TTT GGC GAG GT - #C TGC AGT GGC CAC CTG          1872                                                                        Gln Val Ile Gly Ala Gly Glu Phe Gly Glu Va - #l Cys Ser Gly His Leu                610              - #   615              - #   620                           - - AAG CTG CCA GGC AAG AGA GAG ATC TTT GTG GC - #C ATC AAG ACG CTC AAG          1920                                                                        Lys Leu Pro Gly Lys Arg Glu Ile Phe Val Al - #a Ile Lys Thr Leu Lys            625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - TCG GGC TAC ACG GAG AAG CAG CGC CGG GAC TT - #C CTG AGC GAA GCC         TCC     1968                                                                     Ser Gly Tyr Thr Glu Lys Gln Arg Arg Asp Ph - #e Leu Ser Glu Ala Ser                           645  - #               650  - #               655               - - ATC ATG GGC CAG TTC GAC CAT CCC AAC GTC AT - #C CAC CTG GAG GGT GTC          2016                                                                        Ile Met Gly Gln Phe Asp His Pro Asn Val Il - #e His Leu Glu Gly Val                        660      - #           665      - #           670                   - - GTG ACC AAG AGC ACA CCT GTG ATG ATC ATC AC - #C GAG TTC ATG GAG AAT          2064                                                                        Val Thr Lys Ser Thr Pro Val Met Ile Ile Th - #r Glu Phe Met Glu Asn                    675          - #       680          - #       685                       - - GGC TCC CTG GAC TCC TTT CTC CGG CAA AAC GA - #T GGG CAG TTC ACA GTC          2112                                                                        Gly Ser Leu Asp Ser Phe Leu Arg Gln Asn As - #p Gly Gln Phe Thr Val                690              - #   695              - #   700                           - - ATC CAG CTG GTG GGC ATG CTT CGG GGC ATC GC - #A GCT GGC ATG AAG TAC          2160                                                                        Ile Gln Leu Val Gly Met Leu Arg Gly Ile Al - #a Ala Gly Met Lys Tyr            705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - CTG GCA GAC ATG AAC TAT GTT CAC CGT GAC CT - #G GCT GCC CGC AAC         ATC     2208                                                                     Leu Ala Asp Met Asn Tyr Val His Arg Asp Le - #u Ala Ala Arg Asn Ile                           725  - #               730  - #               735               - - CTC GTC AAC AGC AAC CTG GTC TGC AAG GTG TC - #G GAC TTT GGG CTC TCA          2256                                                                        Leu Val Asn Ser Asn Leu Val Cys Lys Val Se - #r Asp Phe Gly Leu Ser                        740      - #           745      - #           750                   - - CGC TTT CTA GAG GAC GAT ACC TCA GAC CCC AC - #C TAC ACC AGT GCC CTG          2304                                                                        Arg Phe Leu Glu Asp Asp Thr Ser Asp Pro Th - #r Tyr Thr Ser Ala Leu                    755          - #       760          - #       765                       - - GGC GGA AAG TTC CCC ATC CGC TGG ACA GCC CC - #G GAA GCC ATC CAG TAC          2352                                                                        Gly Gly Lys Phe Pro Ile Arg Trp Thr Ala Pr - #o Glu Ala Ile Gln Tyr                770              - #   775              - #   780                           - - CGG AAG TTC ACC TCG GCC AGT GAT GTG TGG AG - #C TAC GGC ATT GTC ATG          2400                                                                        Arg Lys Phe Thr Ser Ala Ser Asp Val Trp Se - #r Tyr Gly Ile Val Met            785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - TGG GAG GTG ATG TCC TAT GGG GAG CGG CCC TA - #C TGG GAC ATG ACC         AAC     2448                                                                     Trp Glu Val Met Ser Tyr Gly Glu Arg Pro Ty - #r Trp Asp Met Thr Asn                           805  - #               810  - #               815               - - CAG GAT GTA ATC AAT GCC ATT GAG CAG GAC TA - #T CGG CTG CCA CCG CCC          2496                                                                        Gln Asp Val Ile Asn Ala Ile Glu Gln Asp Ty - #r Arg Leu Pro Pro Pro                        820      - #           825      - #           830                   - - ATG GAC TGC CCG AGC GCC CTG CAC CAA CTC AT - #G CTG GAC TGT TGG CAG          2544                                                                        Met Asp Cys Pro Ser Ala Leu His Gln Leu Me - #t Leu Asp Cys Trp Gln                    835          - #       840          - #       845                       - - AAG GAC CGC AAC CAC CGG CCC AAG TTC GGC CA - #A ATT GTC AAC ACG CTA          2592                                                                        Lys Asp Arg Asn His Arg Pro Lys Phe Gly Gl - #n Ile Val Asn Thr Leu                850              - #   855              - #   860                           - - GAC AAG ATG ATC CGC AAT CCC AAC AGC CTC AA - #A GCC ATG GCG CCC CTC          2640                                                                        Asp Lys Met Ile Arg Asn Pro Asn Ser Leu Ly - #s Ala Met Ala Pro Leu            865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - TCC TCT GGC ATC AAC CTG CCG CTG CTG GAC CG - #C ACG ATC CCC GAC         TAC     2688                                                                     Ser Ser Gly Ile Asn Leu Pro Leu Leu Asp Ar - #g Thr Ile Pro Asp Tyr                           885  - #               890  - #               895               - - ACC AGC TTT AAC ACG GTG GAC GAG TGG CTG GA - #G GCC ATC AAG ATG GGG          2736                                                                        Thr Ser Phe Asn Thr Val Asp Glu Trp Leu Gl - #u Ala Ile Lys Met Gly                        900      - #           905      - #           910                   - - CAG TAC AAG GAG AGC TTC GCC AAT GCC GGC TT - #C ACC TCC TTT GAC GTC          2784                                                                        Gln Tyr Lys Glu Ser Phe Ala Asn Ala Gly Ph - #e Thr Ser Phe Asp Val                    915          - #       920          - #       925                       - - GTG TCT CAG ATG ATG ATG GAG GAC ATT CTC CG - #G GTT GGG GTC ACT TTG          2832                                                                        Val Ser Gln Met Met Met Glu Asp Ile Leu Ar - #g Val Gly Val Thr Leu                930              - #   935              - #   940                           - - GCT GGC CAC CAG AAA AAA ATC CTG AAC AGT AT - #C CAG GTG ATG CGG GCG          2880                                                                        Ala Gly His Gln Lys Lys Ile Leu Asn Ser Il - #e Gln Val Met Arg Ala            945                 9 - #50                 9 - #55                 9 -       #60                                                                               - - CAG ATG AAC CAG ATT CAG TCT GTG GAG GTT TG - #A CATTCACCTG              CCTCGGCTCA   2933                                                                Gln Met Asn Gln Ile Gln Ser Val Glu Val  - #*                                                  965  - #               970                                      - - CCTCTTCCTC CAAGCCCCGC CCCCTCTGC         - #                  - #               2962                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:11:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  970 ami - #no acids                                               (B) TYPE: amino acid                                                           (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -           (xi) SEQUENCE DESCRIPTION: - # SEQ ID NO:11:                     - - Leu Leu Ala Ala Val Glu Glu Thr Leu Met As - #p Ser Thr Thr Ala Thr         1               5 - #                 10 - #                 15               - - Ala Glu Leu Gly Trp Met Val His Pro Pro Se - #r Gly Trp Glu Glu Val                    20     - #             25     - #             30                   - - Ser Gly Tyr Asp Glu Asn Met Asn Thr Ile Ar - #g Thr Tyr Gln Val Cys                35         - #         40         - #         45                       - - Asn Val Phe Glu Ser Ser Gln Asn Asn Trp Le - #u Arg Thr Lys Phe Ile            50             - #     55             - #     60                           - - Arg Arg Arg Gly Ala His Arg Ile His Val Gl - #u Met Lys Phe Ser Val        65                 - # 70                 - # 75                 - # 80        - - Arg Asp Cys Ser Ser Ile Pro Ser Val Pro Gl - #y Ser Cys Lys Glu Thr                        85 - #                 90 - #                 95               - - Phe Asn Leu Tyr Tyr Tyr Glu Ala Asp Phe As - #p Ser Ala Thr Lys Thr                   100      - #           105      - #           110                   - - Phe Pro Asn Trp Met Glu Asn Pro Trp Val Ly - #s Val Asp Thr Ile Ala               115          - #       120          - #       125                       - - Ala Asp Glu Ser Phe Ser Gln Val Asp Leu Gl - #y Gly Arg Val Met Lys           130              - #   135              - #   140                           - - Ile Asn Thr Glu Val Arg Ser Phe Gly Pro Va - #l Ser Arg Ser Gly Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Tyr Leu Ala Phe Gln Asp Tyr Gly Gly Cys Me - #t Ser Leu Ile Ala         Val                                                                                              165  - #               170  - #               175              - - Arg Val Phe Tyr Arg Lys Cys Pro Arg Ile Il - #e Gln Asn Gly Ala Ile                   180      - #           185      - #           190                   - - Phe Gln Glu Thr Leu Ser Gly Ala Glu Ser Th - #r Ser Leu Val Ala Ala               195          - #       200          - #       205                       - - Arg Gly Ser Cys Ile Ala Asn Ala Glu Glu Va - #l Asp Val Pro Ile Lys           210              - #   215              - #   220                           - - Leu Tyr Cys Asn Gly Asp Gly Glu Trp Leu Va - #l Pro Ile Gly Arg Cys       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Met Cys Lys Ala Gly Phe Glu Ala Val Glu As - #n Gly Thr Val Cys         Arg                                                                                              245  - #               250  - #               255              - - Gly Cys Pro Ser Gly Thr Phe Lys Ala Asn Gl - #n Gly Asp Glu Ala Cys                   260      - #           265      - #           270                   - - Thr His Cys Pro Ile Asn Ser Arg Thr Thr Se - #r Glu Gly Ala Thr Asn               275          - #       280          - #       285                       - - Cys Val Cys Arg Asn Gly Tyr Tyr Arg Ala As - #p Leu Asp Pro Leu Asp           290              - #   295              - #   300                           - - Met Pro Cys Thr Thr Ile Pro Ser Ala Pro Gl - #n Ala Val Ile Ser Ser       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Val Asn Glu Thr Ser Leu Met Leu Glu Trp Th - #r Pro Pro Arg Asp         Ser                                                                                              325  - #               330  - #               335              - - Gly Gly Arg Glu Asp Leu Val Tyr Asn Ile Il - #e Cys Lys Ser Cys Gly                   340      - #           345      - #           350                   - - Ser Gly Arg Gly Ala Cys Thr Arg Cys Gly As - #p Asn Val Gln Tyr Ala               355          - #       360          - #       365                       - - Pro Arg Gln Leu Gly Leu Thr Glu Pro Arg Il - #e Tyr Ile Ser Asp Leu           370              - #   375              - #   380                           - - Leu Ala His Thr Gln Tyr Thr Phe Glu Ile Gl - #n Ala Val Asn Gly Val       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Thr Asp Gln Ser Pro Phe Ser Pro Gln Phe Al - #a Ser Val Asn Ile         Thr                                                                                              405  - #               410  - #               415              - - Thr Asn Gln Ala Ala Pro Ser Ala Val Ser Il - #e Met His Gln Val Ser                   420      - #           425      - #           430                   - - Arg Thr Val Asp Ser Ile Thr Leu Ser Trp Se - #r Gln Pro Asp Gln Pro               435          - #       440          - #       445                       - - Asn Gly Val Ile Leu Asp Tyr Glu Leu Gln Ty - #r Tyr Glu Lys Glu Leu           450              - #   455              - #   460                           - - Ser Glu Tyr Asn Ala Thr Ala Ile Lys Ser Pr - #o Thr Asn Thr Val Thr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Gly Leu Lys Ala Gly Ala Ile Tyr Val Phe Gl - #n Val Arg Ala Arg         Thr                                                                                              485  - #               490  - #               495              - - Val Ala Gly Tyr Gly Arg Tyr Ser Gly Lys Me - #t Tyr Phe Gln Thr Met                   500      - #           505      - #           510                   - - Thr Glu Ala Glu Tyr Gln Thr Ser Ile Gln Gl - #u Lys Leu Pro Leu Ile               515          - #       520          - #       525                       - - Ile Gly Ser Ser Ala Ala Gly Leu Val Phe Le - #u Ile Ala Val Val Val           530              - #   535              - #   540                           - - Ile Ala Ile Val Cys Asn Arg Arg Gly Phe Gl - #u Arg Ala Asp Ser Glu       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Tyr Thr Asp Lys Leu Gln His Tyr Thr Ser Gl - #y His Ile Thr Pro         Gly                                                                                              565  - #               570  - #               575              - - Met Lys Ile Tyr Ile Asp Pro Phe Thr Tyr Gl - #u Asp Pro Asn Glu Ala                   580      - #           585      - #           590                   - - Val Arg Glu Phe Ala Lys Glu Ile Asp Ile Se - #r Cys Val Lys Ile Glu               595          - #       600          - #       605                       - - Gln Val Ile Gly Ala Gly Glu Phe Gly Glu Va - #l Cys Ser Gly His Leu           610              - #   615              - #   620                           - - Lys Leu Pro Gly Lys Arg Glu Ile Phe Val Al - #a Ile Lys Thr Leu Lys       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Ser Gly Tyr Thr Glu Lys Gln Arg Arg Asp Ph - #e Leu Ser Glu Ala         Ser                                                                                              645  - #               650  - #               655              - - Ile Met Gly Gln Phe Asp His Pro Asn Val Il - #e His Leu Glu Gly Val                   660      - #           665      - #           670                   - - Val Thr Lys Ser Thr Pro Val Met Ile Ile Th - #r Glu Phe Met Glu Asn               675          - #       680          - #       685                       - - Gly Ser Leu Asp Ser Phe Leu Arg Gln Asn As - #p Gly Gln Phe Thr Val           690              - #   695              - #   700                           - - Ile Gln Leu Val Gly Met Leu Arg Gly Ile Al - #a Ala Gly Met Lys Tyr       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Leu Ala Asp Met Asn Tyr Val His Arg Asp Le - #u Ala Ala Arg Asn         Ile                                                                                              725  - #               730  - #               735              - - Leu Val Asn Ser Asn Leu Val Cys Lys Val Se - #r Asp Phe Gly Leu Ser                   740      - #           745      - #           750                   - - Arg Phe Leu Glu Asp Asp Thr Ser Asp Pro Th - #r Tyr Thr Ser Ala Leu               755          - #       760          - #       765                       - - Gly Gly Lys Phe Pro Ile Arg Trp Thr Ala Pr - #o Glu Ala Ile Gln Tyr           770              - #   775              - #   780                           - - Arg Lys Phe Thr Ser Ala Ser Asp Val Trp Se - #r Tyr Gly Ile Val Met       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Trp Glu Val Met Ser Tyr Gly Glu Arg Pro Ty - #r Trp Asp Met Thr         Asn                                                                                              805  - #               810  - #               815              - - Gln Asp Val Ile Asn Ala Ile Glu Gln Asp Ty - #r Arg Leu Pro Pro Pro                   820      - #           825      - #           830                   - - Met Asp Cys Pro Ser Ala Leu His Gln Leu Me - #t Leu Asp Cys Trp Gln               835          - #       840          - #       845                       - - Lys Asp Arg Asn His Arg Pro Lys Phe Gly Gl - #n Ile Val Asn Thr Leu           850              - #   855              - #   860                           - - Asp Lys Met Ile Arg Asn Pro Asn Ser Leu Ly - #s Ala Met Ala Pro Leu       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Ser Ser Gly Ile Asn Leu Pro Leu Leu Asp Ar - #g Thr Ile Pro Asp         Tyr                                                                                              885  - #               890  - #               895              - - Thr Ser Phe Asn Thr Val Asp Glu Trp Leu Gl - #u Ala Ile Lys Met Gly                   900      - #           905      - #           910                   - - Gln Tyr Lys Glu Ser Phe Ala Asn Ala Gly Ph - #e Thr Ser Phe Asp Val               915          - #       920          - #       925                       - - Val Ser Gln Met Met Met Glu Asp Ile Leu Ar - #g Val Gly Val Thr Leu           930              - #   935              - #   940                           - - Ala Gly His Gln Lys Lys Ile Leu Asn Ser Il - #e Gln Val Met Arg Ala       945                 9 - #50                 9 - #55                 9 -       #60                                                                               - - Gln Met Asn Gln Ile Gln Ser Val Glu Val                                                   965  - #               970                                      - -  - - (2) INFORMATION FOR SEQ ID NO:12:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 3162 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: 1..2976                                                 - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:12:                        - - CCA GCG TCC CTG GCC GGC TGC TAC TCT GCA CC - #T CGA CGG GCT CCC         CTC       48                                                                     Pro Ala Ser Leu Ala Gly Cys Tyr Ser Ala Pr - #o Arg Arg Ala Pro Leu             1               5 - #                 10 - #                 15               - - TGG ACG TGC CTT CTC CTG TGC GCC GCA CTC CG - #G ACC CTC CTG GCC AGC            96                                                                        Trp Thr Cys Leu Leu Leu Cys Ala Ala Leu Ar - #g Thr Leu Leu Ala Ser                         20     - #             25     - #             30                   - - CCC AGC AAC GAA GTG AAT TTA TTG GAT TCA CG - #C ACT GTC ATG GGG GAC           144                                                                        Pro Ser Asn Glu Val Asn Leu Leu Asp Ser Ar - #g Thr Val Met Gly Asp                     35         - #         40         - #         45                       - - CTG GGA TGG ATT GCT TTT CCA AAA AAT GGG TG - #G GAA GAG ATT GGT GAA           192                                                                        Leu Gly Trp Ile Ala Phe Pro Lys Asn Gly Tr - #p Glu Glu Ile Gly Glu                 50             - #     55             - #     60                           - - GTG GAT GAA AAT TAT GCC CCT ATC CAC ACA TA - #C CAA GTA TGC AAA GTG           240                                                                        Val Asp Glu Asn Tyr Ala Pro Ile His Thr Ty - #r Gln Val Cys Lys Val             65                 - # 70                 - # 75                 - # 80        - - ATG GAA CAG AAT CAG AAT AAC TGG CTT TTG AC - #C AGT TGG ATC TCC AAT           288                                                                        Met Glu Gln Asn Gln Asn Asn Trp Leu Leu Th - #r Ser Trp Ile Ser Asn                             85 - #                 90 - #                 95               - - GAA GGT GCT TCC AGA ATC TTC ATA GAA CTC AA - #A TTT ACC CTG CGG GAC           336                                                                        Glu Gly Ala Ser Arg Ile Phe Ile Glu Leu Ly - #s Phe Thr Leu Arg Asp                        100      - #           105      - #           110                   - - TGC AAC AGC CTT CCT GGA GGA CTG GGG ACC TG - #T AAG GAA ACC TTT AAT           384                                                                        Cys Asn Ser Leu Pro Gly Gly Leu Gly Thr Cy - #s Lys Glu Thr Phe Asn                    115          - #       120          - #       125                       - - ATG TAT TAC TTT GAG TCA GAT GAT CAG AAT GG - #G AGA AAC ATC AAG GAA           432                                                                        Met Tyr Tyr Phe Glu Ser Asp Asp Gln Asn Gl - #y Arg Asn Ile Lys Glu                130              - #   135              - #   140                           - - AAC CAA TAC ATC AAA ATT GAT ACC ATT GCT GC - #C GAT GAA AGC TTT ACA           480                                                                        Asn Gln Tyr Ile Lys Ile Asp Thr Ile Ala Al - #a Asp Glu Ser Phe Thr            145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - GAA CTT GAT CTT GGT GAC CGT GTT ATG AAA CT - #G AAT ACA GAG GTC         AGA      528                                                                     Glu Leu Asp Leu Gly Asp Arg Val Met Lys Le - #u Asn Thr Glu Val Arg                           165  - #               170  - #               175               - - GAT GTA GGA CCT CTA AGC AAA AAG GGA TTT TA - #T CTT GCT TTT CAA GAT           576                                                                        Asp Val Gly Pro Leu Ser Lys Lys Gly Phe Ty - #r Leu Ala Phe Gln Asp                        180      - #           185      - #           190                   - - GTT GGT GCT TGC ATT GCT CTG GTT TCT GTG CG - #T GTA TAC TAT AAA AAA           624                                                                        Val Gly Ala Cys Ile Ala Leu Val Ser Val Ar - #g Val Tyr Tyr Lys Lys                    195          - #       200          - #       205                       - - TGC CCT TCT GTG GTA CGA CAC TTG GCT GTC TT - #C CCT GAC ACC ATC ACT           672                                                                        Cys Pro Ser Val Val Arg His Leu Ala Val Ph - #e Pro Asp Thr Ile Thr                210              - #   215              - #   220                           - - GGA GCT GAT TCT TCC CAA TTG CTC GAA GTG TC - #G GGC TCC TGT GTC AAC           720                                                                        Gly Ala Asp Ser Ser Gln Leu Leu Glu Val Se - #r Gly Ser Cys Val Asn            225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - CAT TCT GTG ACC GAT GAA CCT CCC AAA ATG CA - #C TGC AGC GCC GAA         GGG      768                                                                     His Ser Val Thr Asp Glu Pro Pro Lys Met Hi - #s Cys Ser Ala Glu Gly                           245  - #               250  - #               255               - - GAG TGG CTG GTG CCC ATC GGG AAA TGC ATG TG - #C AAG GCA GGA TAT GAA           816                                                                        Glu Trp Leu Val Pro Ile Gly Lys Cys Met Cy - #s Lys Ala Gly Tyr Glu                        260      - #           265      - #           270                   - - GAG AAA AAT GGC ACC TGT CAA GTG TGC AGA CC - #T GGG TTC TTC AAA GCC           864                                                                        Glu Lys Asn Gly Thr Cys Gln Val Cys Arg Pr - #o Gly Phe Phe Lys Ala                    275          - #       280          - #       285                       - - TCA CCT CAC ATC CAG AGC TGC GGC AAA TGT CC - #A CCT CAC AGT TAT ACC           912                                                                        Ser Pro His Ile Gln Ser Cys Gly Lys Cys Pr - #o Pro His Ser Tyr Thr                290              - #   295              - #   300                           - - CAT GAG GAA GCT TCA ACC TCT TGT GTC TGT GA - #A AAG GAT TAT TTC AGG           960                                                                        His Glu Glu Ala Ser Thr Ser Cys Val Cys Gl - #u Lys Asp Tyr Phe Arg            305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - AGA GAG TCT GAT CCA CCC ACA ATG GCA TGC AC - #A AGA CCC CCC TCT         GCT     1008                                                                     Arg Glu Ser Asp Pro Pro Thr Met Ala Cys Th - #r Arg Pro Pro Ser Ala                           325  - #               330  - #               335               - - CCT CGG AAT GCC ATC TCA AAT GTT AAT GAA AC - #T AGT GTC TTT CTG GAA          1056                                                                        Pro Arg Asn Ala Ile Ser Asn Val Asn Glu Th - #r Ser Val Phe Leu Glu                        340      - #           345      - #           350                   - - TGG ATT CCG CCT GCT GAC ACT GGT GGA AGG AA - #A GAC GTG TCA TAT TAT          1104                                                                        Trp Ile Pro Pro Ala Asp Thr Gly Gly Arg Ly - #s Asp Val Ser Tyr Tyr                    355          - #       360          - #       365                       - - ATT GCA TGC AAG AAG TGC AAC TCC CAT GCA GG - #T GTG TGT GAG GAG TGT          1152                                                                        Ile Ala Cys Lys Lys Cys Asn Ser His Ala Gl - #y Val Cys Glu Glu Cys                370              - #   375              - #   380                           - - GGC GGT CAT GTC AGG TAC CTT CCC CGG CAA AG - #C GGC CTG AAA AAC ACC          1200                                                                        Gly Gly His Val Arg Tyr Leu Pro Arg Gln Se - #r Gly Leu Lys Asn Thr            385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - TCT GTC ATG ATG GTG GAT CTA CTC GCT CAC AC - #A AAC TAT ACC TTT         GAG     1248                                                                     Ser Val Met Met Val Asp Leu Leu Ala His Th - #r Asn Tyr Thr Phe Glu                           405  - #               410  - #               415               - - ATT GAG GCA GTG AAT GGA GTG TCC GAC TTG AG - #C CCA GGA GCC CGG CAG          1296                                                                        Ile Glu Ala Val Asn Gly Val Ser Asp Leu Se - #r Pro Gly Ala Arg Gln                        420      - #           425      - #           430                   - - TAT GTG TCT GTA AAT GTA ACC ACA AAT CAA GC - #A GCT CCA TCT CCA GTC          1344                                                                        Tyr Val Ser Val Asn Val Thr Thr Asn Gln Al - #a Ala Pro Ser Pro Val                    435          - #       440          - #       445                       - - ACC AAT GTG AAA AAA GGG AAA ATT GCA AAA AA - #C AGC ATC TCT TTG TCT          1392                                                                        Thr Asn Val Lys Lys Gly Lys Ile Ala Lys As - #n Ser Ile Ser Leu Ser                450              - #   455              - #   460                           - - TGG CAA GAA CCA GAT CGT CCC AAT GGA ATC AT - #C CTA GAG TAT GAA ATC          1440                                                                        Trp Gln Glu Pro Asp Arg Pro Asn Gly Ile Il - #e Leu Glu Tyr Glu Ile            465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - AAG CAT TTT GAA AAG GAC CAA GAG ACC AGC TA - #C ACG ATT ATC AAA         TCT     1488                                                                     Lys His Phe Glu Lys Asp Gln Glu Thr Ser Ty - #r Thr Ile Ile Lys Ser                           485  - #               490  - #               495               - - AAA GAG ACA ACT ATT ACT GCA GAG GGC TTG AA - #A CCA GCT TCA GTT TAT          1536                                                                        Lys Glu Thr Thr Ile Thr Ala Glu Gly Leu Ly - #s Pro Ala Ser Val Tyr                        500      - #           505      - #           510                   - - GTC TTC CAA ATT CGA GCA CGT ACA GCA GCA GG - #C TAT GGT GTC TTC AGT          1584                                                                        Val Phe Gln Ile Arg Ala Arg Thr Ala Ala Gl - #y Tyr Gly Val Phe Ser                    515          - #       520          - #       525                       - - CGA AGA TTT GAG TTT GAA ACC ACC CCA GTG TT - #T GCA GCA TCC AGC GAT          1632                                                                        Arg Arg Phe Glu Phe Glu Thr Thr Pro Val Ph - #e Ala Ala Ser Ser Asp                530              - #   535              - #   540                           - - CAA AGC CAG ATT CCT GTA ATT GCT GTG TCT GT - #G ACA GTA GGA GTC ATT          1680                                                                        Gln Ser Gln Ile Pro Val Ile Ala Val Ser Va - #l Thr Val Gly Val Ile            545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - TTG TTG GCA GTG GTT ATC GGC GTC CTC CTC AG - #T GGA AGG CGG TGT         GGC     1728                                                                     Leu Leu Ala Val Val Ile Gly Val Leu Leu Se - #r Gly Arg Arg Cys Gly                           565  - #               570  - #               575               - - TAC AGC AAA GCA AAA CAA GAT CCA GAA GAG GA - #A AAG ATG CAT TTT CAT          1776                                                                        Tyr Ser Lys Ala Lys Gln Asp Pro Glu Glu Gl - #u Lys Met His Phe His                        580      - #           585      - #           590                   - - AAT GGG CAC ATT AAA CTG CCA GGA GTA AGA AC - #T TAC ATT GAT CCA CAT          1824                                                                        Asn Gly His Ile Lys Leu Pro Gly Val Arg Th - #r Tyr Ile Asp Pro His                    595          - #       600          - #       605                       - - ACC TAT GAG GAT CCC AAT CAA GCT GTC CAC GA - #A TTT GCC AAG GAG ATA          1872                                                                        Thr Tyr Glu Asp Pro Asn Gln Ala Val His Gl - #u Phe Ala Lys Glu Ile                610              - #   615              - #   620                           - - GAA GCA TCA TGT ATC ACC ATT GAG AGA GTT AT - #T GGA GCA GGT GAA TTT          1920                                                                        Glu Ala Ser Cys Ile Thr Ile Glu Arg Val Il - #e Gly Ala Gly Glu Phe            625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - GGT GAA GTT TGT AGT GGA CGT TTG AAA CTA CC - #A GGA AAA AGA GAA         TTA     1968                                                                     Gly Glu Val Cys Ser Gly Arg Leu Lys Leu Pr - #o Gly Lys Arg Glu Leu                           645  - #               650  - #               655               - - CCT GTG GCT ATC AAA ACC CTT AAA GTA GGC TA - #T ACT GAA AAG CAA CGC          2016                                                                        Pro Val Ala Ile Lys Thr Leu Lys Val Gly Ty - #r Thr Glu Lys Gln Arg                        660      - #           665      - #           670                   - - AGA GAT TTC CTA GGT GAA GCA AGT ATC ATG GG - #A CAG TTT GAT CAT CCT          2064                                                                        Arg Asp Phe Leu Gly Glu Ala Ser Ile Met Gl - #y Gln Phe Asp His Pro                    675          - #       680          - #       685                       - - AAC ATC ATC CAT TTA GAA GGT GTG GTG ACC AA - #A AGT AAA CCA GTG ATG          2112                                                                        Asn Ile Ile His Leu Glu Gly Val Val Thr Ly - #s Ser Lys Pro Val Met                690              - #   695              - #   700                           - - ATC GTG ACA GAG TAT ATG GAG AAT GGC TCT TT - #A GAT ACA TTT TTG AAG          2160                                                                        Ile Val Thr Glu Tyr Met Glu Asn Gly Ser Le - #u Asp Thr Phe Leu Lys            705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - AAA AAC GAT GGG CAG TTC ACT GTG ATT CAG CT - #T GTT GGC ATG CTG         AGA     2208                                                                     Lys Asn Asp Gly Gln Phe Thr Val Ile Gln Le - #u Val Gly Met Leu Arg                           725  - #               730  - #               735               - - GGT ATC TCT GCA GGA ATG AAG TAC CTT TCT GA - #C ATG GGC TAT GTG CAT          2256                                                                        Gly Ile Ser Ala Gly Met Lys Tyr Leu Ser As - #p Met Gly Tyr Val His                        740      - #           745      - #           750                   - - AGA GAT CTT GCT GCC AGA AAC ATC TTA ATC AA - #C AGT AAC CTT GTG TGC          2304                                                                        Arg Asp Leu Ala Ala Arg Asn Ile Leu Ile As - #n Ser Asn Leu Val Cys                    755          - #       760          - #       765                       - - AAA GTG TCT GAC TTT GGA CTT TCC CGG GTA CT - #G GAA GAT GAT CCC GAG          2352                                                                        Lys Val Ser Asp Phe Gly Leu Ser Arg Val Le - #u Glu Asp Asp Pro Glu                770              - #   775              - #   780                           - - GCA GCC TAC ACC ACA AGG GGA GGA AAA ATT CC - #A ATC AGA TGG ACT GCC          2400                                                                        Ala Ala Tyr Thr Thr Arg Gly Gly Lys Ile Pr - #o Ile Arg Trp Thr Ala            785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - CCA GAA GCA ATA GCT TTC CGA AAG TTT ACT TC - #T GCC AGT GAT GTC         TGG     2448                                                                     Pro Glu Ala Ile Ala Phe Arg Lys Phe Thr Se - #r Ala Ser Asp Val Trp                           805  - #               810  - #               815               - - AGT TAT GGA ATA GTA ATG TGG GAA GTT GTG TC - #T TAT GGA GAG AGA CCC          2496                                                                        Ser Tyr Gly Ile Val Met Trp Glu Val Val Se - #r Tyr Gly Glu Arg Pro                        820      - #           825      - #           830                   - - TAC TGG GAG ATG ACC AAT CAA GAT GTG ATT AA - #A GCG GTA GAG GAA GGC          2544                                                                        Tyr Trp Glu Met Thr Asn Gln Asp Val Ile Ly - #s Ala Val Glu Glu Gly                    835          - #       840          - #       845                       - - TAT CGT CTG CCA AGC CCC ATG GAT TGT CCT GC - #T GCT CTC TAT CAG TTA          2592                                                                        Tyr Arg Leu Pro Ser Pro Met Asp Cys Pro Al - #a Ala Leu Tyr Gln Leu                850              - #   855              - #   860                           - - ATG CTG GAT TGC TGG CAG AAA GAG CGA AAT AG - #C AGG CCC AAG TTT GAT          2640                                                                        Met Leu Asp Cys Trp Gln Lys Glu Arg Asn Se - #r Arg Pro Lys Phe Asp            865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - GAA ATA GTC AAC ATG TTG GAC AAG CTG ATA CG - #T AAC CCA AGT AGT         CTG     2688                                                                     Glu Ile Val Asn Met Leu Asp Lys Leu Ile Ar - #g Asn Pro Ser Ser Leu                           885  - #               890  - #               895               - - AAG ACG CTG GTT AAT GCA TCC TGC AGA GTA TC - #T AAT TTA TTG GCA GAA          2736                                                                        Lys Thr Leu Val Asn Ala Ser Cys Arg Val Se - #r Asn Leu Leu Ala Glu                        900      - #           905      - #           910                   - - CAT AGC CCA CTA GGA TCT GGG GCC TAC AGA TC - #A GTA GGT GAA TGG CTA          2784                                                                        His Ser Pro Leu Gly Ser Gly Ala Tyr Arg Se - #r Val Gly Glu Trp Leu                    915          - #       920          - #       925                       - - GAG GCA ATC AAG ATG GGC CGG TAT ACA GAG AT - #T TTC ATG GAA AAT GGA          2832                                                                        Glu Ala Ile Lys Met Gly Arg Tyr Thr Glu Il - #e Phe Met Glu Asn Gly                930              - #   935              - #   940                           - - TAC AGT TCA ATG GAC GCT GTG GCT CAG GTG AC - #C TTG GAG GAT TTG AGA          2880                                                                        Tyr Ser Ser Met Asp Ala Val Ala Gln Val Th - #r Leu Glu Asp Leu Arg            945                 9 - #50                 9 - #55                 9 -       #60                                                                               - - CGG CTT GGA GTG ACT CTT GTC GGT CAC CAG AA - #G AAG ATC ATG AAC         AGC     2928                                                                     Arg Leu Gly Val Thr Leu Val Gly His Gln Ly - #s Lys Ile Met Asn Ser                           965  - #               970  - #               975               - - CTT CAA GAA ATG AAG GTG CAG CTG GTA AAC GG - #A ATG GTG CCA TTG TAA          2976                                                                        Leu Gln Glu Met Lys Val Gln Leu Val Asn Gl - #y Met Val Pro Leu  *                         980      - #           985      - #           990                   - - CTTCATGTAA ATGTCGCTTC TTCAAGTGAA TGATTCTGCA CTTTGTAAAC AG -              #CACTGAGA   3036                                                                  - - TTTATTTTAA CAAAAAAAGG GGGAAAAGGG AAAACAGTGA TTTCTAAACC TT -             #AGAAAACA   3096                                                                  - - TTTGCCTCAG CCACAGAATT TGTAATCATG GTTTTACTGA AGTATCCAGT TC -             #TTAGTCCT   3156                                                                  - - TAGTCT                 - #                  - #                  -      #         3162                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:13:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  991 ami - #no acids                                               (B) TYPE: amino acid                                                           (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -           (xi) SEQUENCE DESCRIPTION: - # SEQ ID NO:13:                     - - Pro Ala Ser Leu Ala Gly Cys Tyr Ser Ala Pr - #o Arg Arg Ala Pro Leu         1               5 - #                 10 - #                 15               - - Trp Thr Cys Leu Leu Leu Cys Ala Ala Leu Ar - #g Thr Leu Leu Ala Ser                    20     - #             25     - #             30                   - - Pro Ser Asn Glu Val Asn Leu Leu Asp Ser Ar - #g Thr Val Met Gly Asp                35         - #         40         - #         45                       - - Leu Gly Trp Ile Ala Phe Pro Lys Asn Gly Tr - #p Glu Glu Ile Gly Glu            50             - #     55             - #     60                           - - Val Asp Glu Asn Tyr Ala Pro Ile His Thr Ty - #r Gln Val Cys Lys Val        65                 - # 70                 - # 75                 - # 80        - - Met Glu Gln Asn Gln Asn Asn Trp Leu Leu Th - #r Ser Trp Ile Ser Asn                        85 - #                 90 - #                 95               - - Glu Gly Ala Ser Arg Ile Phe Ile Glu Leu Ly - #s Phe Thr Leu Arg Asp                   100      - #           105      - #           110                   - - Cys Asn Ser Leu Pro Gly Gly Leu Gly Thr Cy - #s Lys Glu Thr Phe Asn               115          - #       120          - #       125                       - - Met Tyr Tyr Phe Glu Ser Asp Asp Gln Asn Gl - #y Arg Asn Ile Lys Glu           130              - #   135              - #   140                           - - Asn Gln Tyr Ile Lys Ile Asp Thr Ile Ala Al - #a Asp Glu Ser Phe Thr       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Glu Leu Asp Leu Gly Asp Arg Val Met Lys Le - #u Asn Thr Glu Val         Arg                                                                                              165  - #               170  - #               175              - - Asp Val Gly Pro Leu Ser Lys Lys Gly Phe Ty - #r Leu Ala Phe Gln Asp                   180      - #           185      - #           190                   - - Val Gly Ala Cys Ile Ala Leu Val Ser Val Ar - #g Val Tyr Tyr Lys Lys               195          - #       200          - #       205                       - - Cys Pro Ser Val Val Arg His Leu Ala Val Ph - #e Pro Asp Thr Ile Thr           210              - #   215              - #   220                           - - Gly Ala Asp Ser Ser Gln Leu Leu Glu Val Se - #r Gly Ser Cys Val Asn       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - His Ser Val Thr Asp Glu Pro Pro Lys Met Hi - #s Cys Ser Ala Glu         Gly                                                                                              245  - #               250  - #               255              - - Glu Trp Leu Val Pro Ile Gly Lys Cys Met Cy - #s Lys Ala Gly Tyr Glu                   260      - #           265      - #           270                   - - Glu Lys Asn Gly Thr Cys Gln Val Cys Arg Pr - #o Gly Phe Phe Lys Ala               275          - #       280          - #       285                       - - Ser Pro His Ile Gln Ser Cys Gly Lys Cys Pr - #o Pro His Ser Tyr Thr           290              - #   295              - #   300                           - - His Glu Glu Ala Ser Thr Ser Cys Val Cys Gl - #u Lys Asp Tyr Phe Arg       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Arg Glu Ser Asp Pro Pro Thr Met Ala Cys Th - #r Arg Pro Pro Ser         Ala                                                                                              325  - #               330  - #               335              - - Pro Arg Asn Ala Ile Ser Asn Val Asn Glu Th - #r Ser Val Phe Leu Glu                   340      - #           345      - #           350                   - - Trp Ile Pro Pro Ala Asp Thr Gly Gly Arg Ly - #s Asp Val Ser Tyr Tyr               355          - #       360          - #       365                       - - Ile Ala Cys Lys Lys Cys Asn Ser His Ala Gl - #y Val Cys Glu Glu Cys           370              - #   375              - #   380                           - - Gly Gly His Val Arg Tyr Leu Pro Arg Gln Se - #r Gly Leu Lys Asn Thr       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Ser Val Met Met Val Asp Leu Leu Ala His Th - #r Asn Tyr Thr Phe         Glu                                                                                              405  - #               410  - #               415              - - Ile Glu Ala Val Asn Gly Val Ser Asp Leu Se - #r Pro Gly Ala Arg Gln                   420      - #           425      - #           430                   - - Tyr Val Ser Val Asn Val Thr Thr Asn Gln Al - #a Ala Pro Ser Pro Val               435          - #       440          - #       445                       - - Thr Asn Val Lys Lys Gly Lys Ile Ala Lys As - #n Ser Ile Ser Leu Ser           450              - #   455              - #   460                           - - Trp Gln Glu Pro Asp Arg Pro Asn Gly Ile Il - #e Leu Glu Tyr Glu Ile       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Lys His Phe Glu Lys Asp Gln Glu Thr Ser Ty - #r Thr Ile Ile Lys         Ser                                                                                              485  - #               490  - #               495              - - Lys Glu Thr Thr Ile Thr Ala Glu Gly Leu Ly - #s Pro Ala Ser Val Tyr                   500      - #           505      - #           510                   - - Val Phe Gln Ile Arg Ala Arg Thr Ala Ala Gl - #y Tyr Gly Val Phe Ser               515          - #       520          - #       525                       - - Arg Arg Phe Glu Phe Glu Thr Thr Pro Val Ph - #e Ala Ala Ser Ser Asp           530              - #   535              - #   540                           - - Gln Ser Gln Ile Pro Val Ile Ala Val Ser Va - #l Thr Val Gly Val Ile       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Leu Leu Ala Val Val Ile Gly Val Leu Leu Se - #r Gly Arg Arg Cys         Gly                                                                                              565  - #               570  - #               575              - - Tyr Ser Lys Ala Lys Gln Asp Pro Glu Glu Gl - #u Lys Met His Phe His                   580      - #           585      - #           590                   - - Asn Gly His Ile Lys Leu Pro Gly Val Arg Th - #r Tyr Ile Asp Pro His               595          - #       600          - #       605                       - - Thr Tyr Glu Asp Pro Asn Gln Ala Val His Gl - #u Phe Ala Lys Glu Ile           610              - #   615              - #   620                           - - Glu Ala Ser Cys Ile Thr Ile Glu Arg Val Il - #e Gly Ala Gly Glu Phe       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Gly Glu Val Cys Ser Gly Arg Leu Lys Leu Pr - #o Gly Lys Arg Glu         Leu                                                                                              645  - #               650  - #               655              - - Pro Val Ala Ile Lys Thr Leu Lys Val Gly Ty - #r Thr Glu Lys Gln Arg                   660      - #           665      - #           670                   - - Arg Asp Phe Leu Gly Glu Ala Ser Ile Met Gl - #y Gln Phe Asp His Pro               675          - #       680          - #       685                       - - Asn Ile Ile His Leu Glu Gly Val Val Thr Ly - #s Ser Lys Pro Val Met           690              - #   695              - #   700                           - - Ile Val Thr Glu Tyr Met Glu Asn Gly Ser Le - #u Asp Thr Phe Leu Lys       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Lys Asn Asp Gly Gln Phe Thr Val Ile Gln Le - #u Val Gly Met Leu         Arg                                                                                              725  - #               730  - #               735              - - Gly Ile Ser Ala Gly Met Lys Tyr Leu Ser As - #p Met Gly Tyr Val His                   740      - #           745      - #           750                   - - Arg Asp Leu Ala Ala Arg Asn Ile Leu Ile As - #n Ser Asn Leu Val Cys               755          - #       760          - #       765                       - - Lys Val Ser Asp Phe Gly Leu Ser Arg Val Le - #u Glu Asp Asp Pro Glu           770              - #   775              - #   780                           - - Ala Ala Tyr Thr Thr Arg Gly Gly Lys Ile Pr - #o Ile Arg Trp Thr Ala       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Pro Glu Ala Ile Ala Phe Arg Lys Phe Thr Se - #r Ala Ser Asp Val         Trp                                                                                              805  - #               810  - #               815              - - Ser Tyr Gly Ile Val Met Trp Glu Val Val Se - #r Tyr Gly Glu Arg Pro                   820      - #           825      - #           830                   - - Tyr Trp Glu Met Thr Asn Gln Asp Val Ile Ly - #s Ala Val Glu Glu Gly               835          - #       840          - #       845                       - - Tyr Arg Leu Pro Ser Pro Met Asp Cys Pro Al - #a Ala Leu Tyr Gln Leu           850              - #   855              - #   860                           - - Met Leu Asp Cys Trp Gln Lys Glu Arg Asn Se - #r Arg Pro Lys Phe Asp       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Glu Ile Val Asn Met Leu Asp Lys Leu Ile Ar - #g Asn Pro Ser Ser         Leu                                                                                              885  - #               890  - #               895              - - Lys Thr Leu Val Asn Ala Ser Cys Arg Val Se - #r Asn Leu Leu Ala Glu                   900      - #           905      - #           910                   - - His Ser Pro Leu Gly Ser Gly Ala Tyr Arg Se - #r Val Gly Glu Trp Leu               915          - #       920          - #       925                       - - Glu Ala Ile Lys Met Gly Arg Tyr Thr Glu Il - #e Phe Met Glu Asn Gly           930              - #   935              - #   940                           - - Tyr Ser Ser Met Asp Ala Val Ala Gln Val Th - #r Leu Glu Asp Leu Arg       945                 9 - #50                 9 - #55                 9 -       #60                                                                               - - Arg Leu Gly Val Thr Leu Val Gly His Gln Ly - #s Lys Ile Met Asn         Ser                                                                                              965  - #               970  - #               975              - - Leu Gln Glu Met Lys Val Gln Leu Val Asn Gl - #y Met Val Pro Leu                       980      - #           985      - #           990                   - -  - - (2) INFORMATION FOR SEQ ID NO:14:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 3116 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: 34..2994                                                - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:14:                        - - AAGCGGCAGG AGCAGCGTTG GCACCGGCGA ACC ATG GCT GGG AT - #T TTC TAT         TTC      54                                                                                        - #                  - # Met Ala Gly Ile Phe Tyr Phe                          - #                  - #   1               - #5               - - GCC CTA TTT TCG TGT CTC TTC GGG ATT TGC GA - #C GCT GTC ACA GGT TCC           102                                                                        Ala Leu Phe Ser Cys Leu Phe Gly Ile Cys As - #p Ala Val Thr Gly Ser                     10         - #         15         - #         20                       - - AGG GTA TAC CCC GCG AAT GAA GTT ACC TTA TT - #G GAT TCC AGA TCT GTT           150                                                                        Arg Val Tyr Pro Ala Asn Glu Val Thr Leu Le - #u Asp Ser Arg Ser Val                 25             - #     30             - #     35                           - - CAG GGA GAA CTT GGG TGG ATA GCA AGC CCT CT - #G GAA GGA GGG TGG GAG           198                                                                        Gln Gly Glu Leu Gly Trp Ile Ala Ser Pro Le - #u Glu Gly Gly Trp Glu             40                 - # 45                 - # 50                 - # 55        - - GAA GTG AGT ATC ATG GAT GAA AAA AAT ACA CC - #A ATC CGA ACC TAC CAA           246                                                                        Glu Val Ser Ile Met Asp Glu Lys Asn Thr Pr - #o Ile Arg Thr Tyr Gln                             60 - #                 65 - #                 70               - - GTG TGC AAT GTG ATG GAA CCC AGC CAG AAT AA - #C TGG CTA CGA ACT GAT           294                                                                        Val Cys Asn Val Met Glu Pro Ser Gln Asn As - #n Trp Leu Arg Thr Asp                         75     - #             80     - #             85                   - - TGG ATC ACC CGA GAA GGG GCT CAG AGG GTG TA - #T ATT GAG ATT AAA TTC           342                                                                        Trp Ile Thr Arg Glu Gly Ala Gln Arg Val Ty - #r Ile Glu Ile Lys Phe                     90         - #         95         - #        100                       - - ACC TTG AGG GAC TGC AAT AGT CTT CCG GGC GT - #C ATG GGG ACT TGC AAG           390                                                                        Thr Leu Arg Asp Cys Asn Ser Leu Pro Gly Va - #l Met Gly Thr Cys Lys                105              - #   110              - #   115                           - - GAG ACG TTT AAC CTG TAC TAC TAT GAA TCA GA - #C AAC GAC AAA GAG CGT           438                                                                        Glu Thr Phe Asn Leu Tyr Tyr Tyr Glu Ser As - #p Asn Asp Lys Glu Arg            120                 1 - #25                 1 - #30                 1 -       #35                                                                               - - TTC ATC AGA GAG AAC CAG TTT GTC AAA ATT GA - #C ACC ATT GCT GCT         GAT      486                                                                     Phe Ile Arg Glu Asn Gln Phe Val Lys Ile As - #p Thr Ile Ala Ala Asp                           140  - #               145  - #               150               - - GAG AGC TTC ACC CAA GTG GAC ATT GGT GAC AG - #A ATC ATG AAG CTG AAC           534                                                                        Glu Ser Phe Thr Gln Val Asp Ile Gly Asp Ar - #g Ile Met Lys Leu Asn                        155      - #           160      - #           165                   - - ACC GAG ATC CGG GAT GTA GGG CCA TTA AGC AA - #A AAG GGG TTT TAC CTG           582                                                                        Thr Glu Ile Arg Asp Val Gly Pro Leu Ser Ly - #s Lys Gly Phe Tyr Leu                    170          - #       175          - #       180                       - - GCT TTT CAG GAT GTG GGG GCC TGC ATC GCC CT - #G GTA TCA GTC CGT GTG           630                                                                        Ala Phe Gln Asp Val Gly Ala Cys Ile Ala Le - #u Val Ser Val Arg Val                185              - #   190              - #   195                           - - TTC TAT AAA AAG TGT CCA CTC ACA GTC CGC AA - #T CTG GCC CAG TTT CCT           678                                                                        Phe Tyr Lys Lys Cys Pro Leu Thr Val Arg As - #n Leu Ala Gln Phe Pro            200                 2 - #05                 2 - #10                 2 -       #15                                                                               - - GAC ACC ATC ACA GGG GCT GAT ACG TCT TCC CT - #G GTG GAA GTT CGA         GGC      726                                                                     Asp Thr Ile Thr Gly Ala Asp Thr Ser Ser Le - #u Val Glu Val Arg Gly                           220  - #               225  - #               230               - - TCC TGT GTC AAC AAC TCA GAA GAG AAA GAT GT - #G CCA AAA ATG TAC TGT           774                                                                        Ser Cys Val Asn Asn Ser Glu Glu Lys Asp Va - #l Pro Lys Met Tyr Cys                        235      - #           240      - #           245                   - - GGG GCA GAT GGT GAA TGG CTG GTA CCC ATT GG - #C AAC TGC CTA TGC AAC           822                                                                        Gly Ala Asp Gly Glu Trp Leu Val Pro Ile Gl - #y Asn Cys Leu Cys Asn                    250          - #       255          - #       260                       - - GCT GGG CAT GAG GAG CGG AGC GGA GAA TGC CA - #A GCT TGC AAA ATT GGA           870                                                                        Ala Gly His Glu Glu Arg Ser Gly Glu Cys Gl - #n Ala Cys Lys Ile Gly                265              - #   270              - #   275                           - - TAT TAC AAG GCT CTC TCC ACG GAT GCC ACC TG - #T GCC AAG TGC CCA CCC           918                                                                        Tyr Tyr Lys Ala Leu Ser Thr Asp Ala Thr Cy - #s Ala Lys Cys Pro Pro            280                 2 - #85                 2 - #90                 2 -       #95                                                                               - - CAC AGC TAC TCT GTC TGG GAA GGA GCC ACC TC - #G TGC ACC TGT GAC         CGA      966                                                                     His Ser Tyr Ser Val Trp Glu Gly Ala Thr Se - #r Cys Thr Cys Asp Arg                           300  - #               305  - #               310               - - GGC TTT TTC AGA GCT GAC AAC GAT GCT GCC TC - #T ATG CCC TGC ACC CGT          1014                                                                        Gly Phe Phe Arg Ala Asp Asn Asp Ala Ala Se - #r Met Pro Cys Thr Arg                        315      - #           320      - #           325                   - - CCA CCA TCT GCT CCC CTG AAC TTG ATT TCA AA - #T GTC AAC GAG ACA TCT          1062                                                                        Pro Pro Ser Ala Pro Leu Asn Leu Ile Ser As - #n Val Asn Glu Thr Ser                    330          - #       335          - #       340                       - - GTG AAC TTG GAA TGG AGT AGC CCT CAG AAT AC - #A GGT GGC CGC CAG GAC          1110                                                                        Val Asn Leu Glu Trp Ser Ser Pro Gln Asn Th - #r Gly Gly Arg Gln Asp                345              - #   350              - #   355                           - - ATT TCC TAT AAT GTG GTA TGC AAG AAA TGT GG - #A GCT GGT GAC CCC AGC          1158                                                                        Ile Ser Tyr Asn Val Val Cys Lys Lys Cys Gl - #y Ala Gly Asp Pro Ser            360                 3 - #65                 3 - #70                 3 -       #75                                                                               - - AAG TGC CGA CCC TGT GGA AGT GGG GTC CAC TA - #C ACC CCA CAG CAG         AAT     1206                                                                     Lys Cys Arg Pro Cys Gly Ser Gly Val His Ty - #r Thr Pro Gln Gln Asn                           380  - #               385  - #               390               - - GGC TTG AAG ACC ACC AAA GTC TCC ATC ACT GA - #C CTC CTA GCT CAT ACC          1254                                                                        Gly Leu Lys Thr Thr Lys Val Ser Ile Thr As - #p Leu Leu Ala His Thr                        395      - #           400      - #           405                   - - AAT TAC ACC TTT GAA ATC TGG GCT GTG AAT GG - #A GTG TCC AAA TAT AAC          1302                                                                        Asn Tyr Thr Phe Glu Ile Trp Ala Val Asn Gl - #y Val Ser Lys Tyr Asn                    410          - #       415          - #       420                       - - CCT AAC CCA GAC CAA TCA GTT TCT GTC ACT GT - #G ACC ACC AAC CAA GCA          1350                                                                        Pro Asn Pro Asp Gln Ser Val Ser Val Thr Va - #l Thr Thr Asn Gln Ala                425              - #   430              - #   435                           - - GCA CCA TCA TCC ATT GCT TTG GTC CAG GCT AA - #A GAA GTC ACA AGA TAC          1398                                                                        Ala Pro Ser Ser Ile Ala Leu Val Gln Ala Ly - #s Glu Val Thr Arg Tyr            440                 4 - #45                 4 - #50                 4 -       #55                                                                               - - AGT GTG GCA CTG GCT TGG CTG GAA CCA GAT CG - #G CCC AAT GGG GTA         ATC     1446                                                                     Ser Val Ala Leu Ala Trp Leu Glu Pro Asp Ar - #g Pro Asn Gly Val Ile                           460  - #               465  - #               470               - - CTG GAA TAT GAA GTC AAG TAT TAT GAG AAG GA - #T CAG AAT GAG CGA AGC          1494                                                                        Leu Glu Tyr Glu Val Lys Tyr Tyr Glu Lys As - #p Gln Asn Glu Arg Ser                        475      - #           480      - #           485                   - - TAT CGT ATA GTT CGG ACA GCT GCC AGG AAC AC - #A GAT ATC AAA GGC CTG          1542                                                                        Tyr Arg Ile Val Arg Thr Ala Ala Arg Asn Th - #r Asp Ile Lys Gly Leu                    490          - #       495          - #       500                       - - AAC CCT CTC ACT TCC TAT GTT TTC CAC GTG CG - #A GCC AGG ACA GCA GCT          1590                                                                        Asn Pro Leu Thr Ser Tyr Val Phe His Val Ar - #g Ala Arg Thr Ala Ala                505              - #   510              - #   515                           - - GGC TAT GGA GAC TTC AGT GAG CCC TTG GAG GT - #T ACA ACC AAC ACA GTG          1638                                                                        Gly Tyr Gly Asp Phe Ser Glu Pro Leu Glu Va - #l Thr Thr Asn Thr Val            520                 5 - #25                 5 - #30                 5 -       #35                                                                               - - CCT TCC CGG ATC ATT GGA GAT GGG GCT AAC TC - #C ACA GTC CTT CTG         GTC     1686                                                                     Pro Ser Arg Ile Ile Gly Asp Gly Ala Asn Se - #r Thr Val Leu Leu Val                           540  - #               545  - #               550               - - TCT GTC TCG GGC AGT GTG GTG CTG GTG GTA AT - #T CTC ATT GCA GCT TTT          1734                                                                        Ser Val Ser Gly Ser Val Val Leu Val Val Il - #e Leu Ile Ala Ala Phe                        555      - #           560      - #           565                   - - GTC ATC AGC CGG AGA CGG AGT AAA TAC AGT AA - #A GCC AAA CAA GAA GCG          1782                                                                        Val Ile Ser Arg Arg Arg Ser Lys Tyr Ser Ly - #s Ala Lys Gln Glu Ala                    570          - #       575          - #       580                       - - GAT GAA GAG AAA CAT TTG AAT CAA GGT GTA AG - #A ACA TAT GTG GAC CCC          1830                                                                        Asp Glu Glu Lys His Leu Asn Gln Gly Val Ar - #g Thr Tyr Val Asp Pro                585              - #   590              - #   595                           - - TTT ACG TAC GAA GAT CCC AAC CAA GCA GTG CG - #A GAG TTT GCC AAA GAA          1878                                                                        Phe Thr Tyr Glu Asp Pro Asn Gln Ala Val Ar - #g Glu Phe Ala Lys Glu            600                 6 - #05                 6 - #10                 6 -       #15                                                                               - - ATT GAC GCA TCC TGC ATT AAG ATT GAA AAA GT - #T ATA GGA GTT GGT         GAA     1926                                                                     Ile Asp Ala Ser Cys Ile Lys Ile Glu Lys Va - #l Ile Gly Val Gly Glu                           620  - #               625  - #               630               - - TTT GGT GAG GTA TGC AGT GGG CGT CTC AAA GT - #G CCT GGC AAG AGA GAG          1974                                                                        Phe Gly Glu Val Cys Ser Gly Arg Leu Lys Va - #l Pro Gly Lys Arg Glu                        635      - #           640      - #           645                   - - ATC TGT GTG GCT ATC AAG ACT CTG AAA GCT GG - #T TAT ACA GAC AAA CAG          2022                                                                        Ile Cys Val Ala Ile Lys Thr Leu Lys Ala Gl - #y Tyr Thr Asp Lys Gln                    650          - #       655          - #       660                       - - AGG AGA GAC TTC CTG AGT GAG GCC AGC ATC AT - #G GGA CAG TTT GAC CAT          2070                                                                        Arg Arg Asp Phe Leu Ser Glu Ala Ser Ile Me - #t Gly Gln Phe Asp His                665              - #   670              - #   675                           - - CCG AAC ATC ATT CAC TTG GAA GGC GTG GTC AC - #T AAA TGT AAA CCA GTA          2118                                                                        Pro Asn Ile Ile His Leu Glu Gly Val Val Th - #r Lys Cys Lys Pro Val            680                 6 - #85                 6 - #90                 6 -       #95                                                                               - - ATG ATC ATA ACA GAG TAC ATG GAG AAT GGC TC - #C TTG GAT GCA TTC         CTC     2166                                                                     Met Ile Ile Thr Glu Tyr Met Glu Asn Gly Se - #r Leu Asp Ala Phe Leu                           700  - #               705  - #               710               - - AGG AAA AAT GAT GGC AGA TTT ACA GTC ATT CA - #G CTG GTG GGC ATG CTT          2214                                                                        Arg Lys Asn Asp Gly Arg Phe Thr Val Ile Gl - #n Leu Val Gly Met Leu                        715      - #           720      - #           725                   - - CGT GGC ATT GGG TCT GGG ATG AAG TAT TTA TC - #T GAT ATG AGC TAT GTG          2262                                                                        Arg Gly Ile Gly Ser Gly Met Lys Tyr Leu Se - #r Asp Met Ser Tyr Val                    730          - #       735          - #       740                       - - CAT CGT GAT CTG GCC GCA CGG AAC ATC CTG GT - #G AAC AGC AAC TTG GTC          2310                                                                        His Arg Asp Leu Ala Ala Arg Asn Ile Leu Va - #l Asn Ser Asn Leu Val                745              - #   750              - #   755                           - - TGC AAA GTG TCT GAT TTT GGC ATG TCC CGA GT - #G CTT GAG GAT GAT CCG          2358                                                                        Cys Lys Val Ser Asp Phe Gly Met Ser Arg Va - #l Leu Glu Asp Asp Pro            760                 7 - #65                 7 - #70                 7 -       #75                                                                               - - GAA GCA GCT TAC ACC ACC AGG GGT GGC AAG AT - #T CCT ATC CGG TGG         ACT     2406                                                                     Glu Ala Ala Tyr Thr Thr Arg Gly Gly Lys Il - #e Pro Ile Arg Trp Thr                           780  - #               785  - #               790               - - GCG CCA GAA GCA ATT GCC TAT CGT AAA TTC AC - #A TCA GCA AGT GAT GTA          2454                                                                        Ala Pro Glu Ala Ile Ala Tyr Arg Lys Phe Th - #r Ser Ala Ser Asp Val                        795      - #           800      - #           805                   - - TGG AGC TAT GGA ATC GTT ATG TGG GAA GTG AT - #G TCG TAC GGG GAG AGG          2502                                                                        Trp Ser Tyr Gly Ile Val Met Trp Glu Val Me - #t Ser Tyr Gly Glu Arg                    810          - #       815          - #       820                       - - CCC TAT TGG GAT ATG TCC AAT CAA GAT GTG AT - #T AAA GCC ATT GAG GAA          2550                                                                        Pro Tyr Trp Asp Met Ser Asn Gln Asp Val Il - #e Lys Ala Ile Glu Glu                825              - #   830              - #   835                           - - GGC TAT CGG TTA CCC CCT CCA ATG GAC TGC CC - #C ATT GCG CTC CAC CAG          2598                                                                        Gly Tyr Arg Leu Pro Pro Pro Met Asp Cys Pr - #o Ile Ala Leu His Gln            840                 8 - #45                 8 - #50                 8 -       #55                                                                               - - CTG ATG CTA GAC TGC TGG CAG AAG GAG AGG AG - #C GAC AGG CCT AAA         TTT     2646                                                                     Leu Met Leu Asp Cys Trp Gln Lys Glu Arg Se - #r Asp Arg Pro Lys Phe                           860  - #               865  - #               870               - - GGG CAG ATT GTC AAC ATG TTG GAC AAA CTC AT - #C CGC AAC CCC AAC AGC          2694                                                                        Gly Gln Ile Val Asn Met Leu Asp Lys Leu Il - #e Arg Asn Pro Asn Ser                        875      - #           880      - #           885                   - - TTG AAG AGG ACA GGG ACG GAG AGC TCC AGA CC - #T AAC ACT GCC TTG TTG          2742                                                                        Leu Lys Arg Thr Gly Thr Glu Ser Ser Arg Pr - #o Asn Thr Ala Leu Leu                    890          - #       895          - #       900                       - - GAT CCA AGC TCC CCT GAA TTC TCT GCT GTG GT - #A TCA GTG GGC GAT TGG          2790                                                                        Asp Pro Ser Ser Pro Glu Phe Ser Ala Val Va - #l Ser Val Gly Asp Trp                905              - #   910              - #   915                           - - CTC CAG GCC ATT AAA ATG GAC CGG TAT AAG GA - #T AAC TTC ACA GCT GCT          2838                                                                        Leu Gln Ala Ile Lys Met Asp Arg Tyr Lys As - #p Asn Phe Thr Ala Ala            920                 9 - #25                 9 - #30                 9 -       #35                                                                               - - GGT TAT ACC ACA CTA GAG GCT GTG GTG CAC GT - #G AAC CAG GAG GAC         CTG     2886                                                                     Gly Tyr Thr Thr Leu Glu Ala Val Val His Va - #l Asn Gln Glu Asp Leu                           940  - #               945  - #               950               - - GCA AGA ATT GGT ATC ACA GCC ATC ACG CAC CA - #G AAT AAG ATT TTG AGC          2934                                                                        Ala Arg Ile Gly Ile Thr Ala Ile Thr His Gl - #n Asn Lys Ile Leu Ser                        955      - #           960      - #           965                   - - AGT GTC CAG GCA ATG CGA ACC CAA ATG CAG CA - #G ATG CAC GGC AGA ATG          2982                                                                        Ser Val Gln Ala Met Arg Thr Gln Met Gln Gl - #n Met His Gly Arg Met                    970          - #       975          - #       980                       - - GTT CCC GTC TGA GCCAGTACTG AATAAACTCA AAACTCTTGA AA - #TTAGTTTA              3034                                                                        Val Pro Val  *                                                                     985                                                                         - - CCTCATCCAT GCACTTTAAT TGAAGAACTG CACTTTTTTT ACTTCGTCTT CG -              #CCCTCTGA   3094                                                                  - - AATTAAAGAA ATGAAAAAAA AA           - #                  - #                    3116                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:15:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  986 ami - #no acids                                               (B) TYPE: amino acid                                                           (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -           (xi) SEQUENCE DESCRIPTION: - # SEQ ID NO:15:                     - - Met Ala Gly Ile Phe Tyr Phe Ala Leu Phe Se - #r Cys Leu Phe Gly Ile         1               5 - #                 10 - #                 15               - - Cys Asp Ala Val Thr Gly Ser Arg Val Tyr Pr - #o Ala Asn Glu Val Thr                    20     - #             25     - #             30                   - - Leu Leu Asp Ser Arg Ser Val Gln Gly Glu Le - #u Gly Trp Ile Ala Ser                35         - #         40         - #         45                       - - Pro Leu Glu Gly Gly Trp Glu Glu Val Ser Il - #e Met Asp Glu Lys Asn            50             - #     55             - #     60                           - - Thr Pro Ile Arg Thr Tyr Gln Val Cys Asn Va - #l Met Glu Pro Ser Gln        65                 - # 70                 - # 75                 - # 80        - - Asn Asn Trp Leu Arg Thr Asp Trp Ile Thr Ar - #g Glu Gly Ala Gln Arg                        85 - #                 90 - #                 95               - - Val Tyr Ile Glu Ile Lys Phe Thr Leu Arg As - #p Cys Asn Ser Leu Pro                   100      - #           105      - #           110                   - - Gly Val Met Gly Thr Cys Lys Glu Thr Phe As - #n Leu Tyr Tyr Tyr Glu               115          - #       120          - #       125                       - - Ser Asp Asn Asp Lys Glu Arg Phe Ile Arg Gl - #u Asn Gln Phe Val Lys           130              - #   135              - #   140                           - - Ile Asp Thr Ile Ala Ala Asp Glu Ser Phe Th - #r Gln Val Asp Ile Gly       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Asp Arg Ile Met Lys Leu Asn Thr Glu Ile Ar - #g Asp Val Gly Pro         Leu                                                                                              165  - #               170  - #               175              - - Ser Lys Lys Gly Phe Tyr Leu Ala Phe Gln As - #p Val Gly Ala Cys Ile                   180      - #           185      - #           190                   - - Ala Leu Val Ser Val Arg Val Phe Tyr Lys Ly - #s Cys Pro Leu Thr Val               195          - #       200          - #       205                       - - Arg Asn Leu Ala Gln Phe Pro Asp Thr Ile Th - #r Gly Ala Asp Thr Ser           210              - #   215              - #   220                           - - Ser Leu Val Glu Val Arg Gly Ser Cys Val As - #n Asn Ser Glu Glu Lys       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Asp Val Pro Lys Met Tyr Cys Gly Ala Asp Gl - #y Glu Trp Leu Val         Pro                                                                                              245  - #               250  - #               255              - - Ile Gly Asn Cys Leu Cys Asn Ala Gly His Gl - #u Glu Arg Ser Gly Glu                   260      - #           265      - #           270                   - - Cys Gln Ala Cys Lys Ile Gly Tyr Tyr Lys Al - #a Leu Ser Thr Asp Ala               275          - #       280          - #       285                       - - Thr Cys Ala Lys Cys Pro Pro His Ser Tyr Se - #r Val Trp Glu Gly Ala           290              - #   295              - #   300                           - - Thr Ser Cys Thr Cys Asp Arg Gly Phe Phe Ar - #g Ala Asp Asn Asp Ala       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ala Ser Met Pro Cys Thr Arg Pro Pro Ser Al - #a Pro Leu Asn Leu         Ile                                                                                              325  - #               330  - #               335              - - Ser Asn Val Asn Glu Thr Ser Val Asn Leu Gl - #u Trp Ser Ser Pro Gln                   340      - #           345      - #           350                   - - Asn Thr Gly Gly Arg Gln Asp Ile Ser Tyr As - #n Val Val Cys Lys Lys               355          - #       360          - #       365                       - - Cys Gly Ala Gly Asp Pro Ser Lys Cys Arg Pr - #o Cys Gly Ser Gly Val           370              - #   375              - #   380                           - - His Tyr Thr Pro Gln Gln Asn Gly Leu Lys Th - #r Thr Lys Val Ser Ile       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Thr Asp Leu Leu Ala His Thr Asn Tyr Thr Ph - #e Glu Ile Trp Ala         Val                                                                                              405  - #               410  - #               415              - - Asn Gly Val Ser Lys Tyr Asn Pro Asn Pro As - #p Gln Ser Val Ser Val                   420      - #           425      - #           430                   - - Thr Val Thr Thr Asn Gln Ala Ala Pro Ser Se - #r Ile Ala Leu Val Gln               435          - #       440          - #       445                       - - Ala Lys Glu Val Thr Arg Tyr Ser Val Ala Le - #u Ala Trp Leu Glu Pro           450              - #   455              - #   460                           - - Asp Arg Pro Asn Gly Val Ile Leu Glu Tyr Gl - #u Val Lys Tyr Tyr Glu       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Lys Asp Gln Asn Glu Arg Ser Tyr Arg Ile Va - #l Arg Thr Ala Ala         Arg                                                                                              485  - #               490  - #               495              - - Asn Thr Asp Ile Lys Gly Leu Asn Pro Leu Th - #r Ser Tyr Val Phe His                   500      - #           505      - #           510                   - - Val Arg Ala Arg Thr Ala Ala Gly Tyr Gly As - #p Phe Ser Glu Pro Leu               515          - #       520          - #       525                       - - Glu Val Thr Thr Asn Thr Val Pro Ser Arg Il - #e Ile Gly Asp Gly Ala           530              - #   535              - #   540                           - - Asn Ser Thr Val Leu Leu Val Ser Val Ser Gl - #y Ser Val Val Leu Val       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Val Ile Leu Ile Ala Ala Phe Val Ile Ser Ar - #g Arg Arg Ser Lys         Tyr                                                                                              565  - #               570  - #               575              - - Ser Lys Ala Lys Gln Glu Ala Asp Glu Glu Ly - #s His Leu Asn Gln Gly                   580      - #           585      - #           590                   - - Val Arg Thr Tyr Val Asp Pro Phe Thr Tyr Gl - #u Asp Pro Asn Gln Ala               595          - #       600          - #       605                       - - Val Arg Glu Phe Ala Lys Glu Ile Asp Ala Se - #r Cys Ile Lys Ile Glu           610              - #   615              - #   620                           - - Lys Val Ile Gly Val Gly Glu Phe Gly Glu Va - #l Cys Ser Gly Arg Leu       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Lys Val Pro Gly Lys Arg Glu Ile Cys Val Al - #a Ile Lys Thr Leu         Lys                                                                                              645  - #               650  - #               655              - - Ala Gly Tyr Thr Asp Lys Gln Arg Arg Asp Ph - #e Leu Ser Glu Ala Ser                   660      - #           665      - #           670                   - - Ile Met Gly Gln Phe Asp His Pro Asn Ile Il - #e His Leu Glu Gly Val               675          - #       680          - #       685                       - - Val Thr Lys Cys Lys Pro Val Met Ile Ile Th - #r Glu Tyr Met Glu Asn           690              - #   695              - #   700                           - - Gly Ser Leu Asp Ala Phe Leu Arg Lys Asn As - #p Gly Arg Phe Thr Val       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Ile Gln Leu Val Gly Met Leu Arg Gly Ile Gl - #y Ser Gly Met Lys         Tyr                                                                                              725  - #               730  - #               735              - - Leu Ser Asp Met Ser Tyr Val His Arg Asp Le - #u Ala Ala Arg Asn Ile                   740      - #           745      - #           750                   - - Leu Val Asn Ser Asn Leu Val Cys Lys Val Se - #r Asp Phe Gly Met Ser               755          - #       760          - #       765                       - - Arg Val Leu Glu Asp Asp Pro Glu Ala Ala Ty - #r Thr Thr Arg Gly Gly           770              - #   775              - #   780                           - - Lys Ile Pro Ile Arg Trp Thr Ala Pro Glu Al - #a Ile Ala Tyr Arg Lys       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Phe Thr Ser Ala Ser Asp Val Trp Ser Tyr Gl - #y Ile Val Met Trp         Glu                                                                                              805  - #               810  - #               815              - - Val Met Ser Tyr Gly Glu Arg Pro Tyr Trp As - #p Met Ser Asn Gln Asp                   820      - #           825      - #           830                   - - Val Ile Lys Ala Ile Glu Glu Gly Tyr Arg Le - #u Pro Pro Pro Met Asp               835          - #       840          - #       845                       - - Cys Pro Ile Ala Leu His Gln Leu Met Leu As - #p Cys Trp Gln Lys Glu           850              - #   855              - #   860                           - - Arg Ser Asp Arg Pro Lys Phe Gly Gln Ile Va - #l Asn Met Leu Asp Lys       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Leu Ile Arg Asn Pro Asn Ser Leu Lys Arg Th - #r Gly Thr Glu Ser         Ser                                                                                              885  - #               890  - #               895              - - Arg Pro Asn Thr Ala Leu Leu Asp Pro Ser Se - #r Pro Glu Phe Ser Ala                   900      - #           905      - #           910                   - - Val Val Ser Val Gly Asp Trp Leu Gln Ala Il - #e Lys Met Asp Arg Tyr               915          - #       920          - #       925                       - - Lys Asp Asn Phe Thr Ala Ala Gly Tyr Thr Th - #r Leu Glu Ala Val Val           930              - #   935              - #   940                           - - His Val Asn Gln Glu Asp Leu Ala Arg Ile Gl - #y Ile Thr Ala Ile Thr       945                 9 - #50                 9 - #55                 9 -       #60                                                                               - - His Gln Asn Lys Ile Leu Ser Ser Val Gln Al - #a Met Arg Thr Gln         Met                                                                                              965  - #               970  - #               975              - - Gln Gln Met His Gly Arg Met Val Pro Val                                               980      - #           985                                          - -  - - (2) INFORMATION FOR SEQ ID NO:16:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 4529 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: 186..3182                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:16:                        - - CGGTGCGAGC GAACAGGAGT GGGGGGGAAA TTAAAAAAAG CTAAACGTGG AG -              #CAGCCGAT     60                                                                  - - CGGGGACCGA GAAGGGGAAT CGATGCAAGG AGCACACTAA AACAAAAGCT AC -             #TTCGGAAC    120                                                                  - - AAACAGCATT TAAAAATCCA CGACTCAAGA TAACTGAAAC CTAAAATAAA AC -             #CTGCTCAT    180                                                                  - - GCACC ATG GTT TTT CAA ACT CGG TAC CCT TCA - #TGG ATT ATT TTA TGC             227                                                                              Met Val Phe Gln Thr Arg Tyr - #Pro Ser Trp Ile Ile Leu Cys                       1          - #     5             - #     10                             - - TAC ATC TGG CTG CTC CGC TTT GCA CAC ACA GG - #G GAG GCG CAG GCT GCG           275                                                                        Tyr Ile Trp Leu Leu Arg Phe Ala His Thr Gl - #y Glu Ala Gln Ala Ala             15                 - # 20                 - # 25                 - # 30        - - AAG GAA GTA CTA CTG CTG GAT TCT AAA GCA CA - #A CAA ACA GAG TTG GAG           323                                                                        Lys Glu Val Leu Leu Leu Asp Ser Lys Ala Gl - #n Gln Thr Glu Leu Glu                             35 - #                 40 - #                 45               - - TGG ATT TCC TCT CCA CCC AAT GGG TGG GAA GA - #A ATT AGT GGT TTG GAT           371                                                                        Trp Ile Ser Ser Pro Pro Asn Gly Trp Glu Gl - #u Ile Ser Gly Leu Asp                         50     - #             55     - #             60                   - - GAG AAC TAT ACC CCG ATA CGA ACA TAC CAG GT - #G TGC CAA GTC ATG GAG           419                                                                        Glu Asn Tyr Thr Pro Ile Arg Thr Tyr Gln Va - #l Cys Gln Val Met Glu                     65         - #         70         - #         75                       - - CCC AAC CAA AAC AAC TGG CTG CGG ACT AAC TG - #G ATT TCC AAA GGC AAT           467                                                                        Pro Asn Gln Asn Asn Trp Leu Arg Thr Asn Tr - #p Ile Ser Lys Gly Asn                 80             - #     85             - #     90                           - - GCA CAA AGG ATT TTT GTA GAA TTG AAA TTC AC - #C CTG AGG GAT TGT AAC           515                                                                        Ala Gln Arg Ile Phe Val Glu Leu Lys Phe Th - #r Leu Arg Asp Cys Asn             95                 - #100                 - #105                 - #110        - - AGT CTT CCT GGA GTA CTG GGA ACT TGC AAG GA - #A ACA TTT AAT TTG TAC           563                                                                        Ser Leu Pro Gly Val Leu Gly Thr Cys Lys Gl - #u Thr Phe Asn Leu Tyr                            115  - #               120  - #               125               - - TAT TAT GAA ACA GAC TAT GAC ACT GGC AGG AA - #T ATA AGA GAA AAC CTC           611                                                                        Tyr Tyr Glu Thr Asp Tyr Asp Thr Gly Arg As - #n Ile Arg Glu Asn Leu                        130      - #           135      - #           140                   - - TAT GTA AAA ATA GAC ACC ATT GCT GCA GAT GA - #A AGT TTT ACC CAA GGT           659                                                                        Tyr Val Lys Ile Asp Thr Ile Ala Ala Asp Gl - #u Ser Phe Thr Gln Gly                    145          - #       150          - #       155                       - - GAC CTT GGT GAA AGA AAG ATG AAG CTT AAC AC - #T GAG GTG AGA GAG ATT           707                                                                        Asp Leu Gly Glu Arg Lys Met Lys Leu Asn Th - #r Glu Val Arg Glu Ile                160              - #   165              - #   170                           - - GGA CCT TTG TCC AAA AAG GGA TTC TAT CTT GC - #C TTT CAG GAT GTA GGG           755                                                                        Gly Pro Leu Ser Lys Lys Gly Phe Tyr Leu Al - #a Phe Gln Asp Val Gly            175                 1 - #80                 1 - #85                 1 -       #90                                                                               - - GCT TGC ATA GCT TTG GTT TCT GTC AAA GTG TA - #C TAC AAG AAG TGC         TGG      803                                                                     Ala Cys Ile Ala Leu Val Ser Val Lys Val Ty - #r Tyr Lys Lys Cys Trp                           195  - #               200  - #               205               - - TCC ATT ATT GAG AAC TTA GCT ATC TTT CCA GA - #T ACA GTG ACT GGT TCA           851                                                                        Ser Ile Ile Glu Asn Leu Ala Ile Phe Pro As - #p Thr Val Thr Gly Ser                        210      - #           215      - #           220                   - - GAA TTT TCC TCT TTA GTC GAG GTT CGA GGG AC - #A TGT GTC AGC AGT GCA           899                                                                        Glu Phe Ser Ser Leu Val Glu Val Arg Gly Th - #r Cys Val Ser Ser Ala                    225          - #       230          - #       235                       - - GAG GAA GAA GCG GAA AAC GCC CCC AGG ATG CA - #C TGC AGT GCA GAA GGA           947                                                                        Glu Glu Glu Ala Glu Asn Ala Pro Arg Met Hi - #s Cys Ser Ala Glu Gly                240              - #   245              - #   250                           - - GAA TGG TTA GTG CCC ATT GGA AAA TGT ATC TG - #C AAA GCA GGC TAC CAG           995                                                                        Glu Trp Leu Val Pro Ile Gly Lys Cys Ile Cy - #s Lys Ala Gly Tyr Gln            255                 2 - #60                 2 - #65                 2 -       #70                                                                               - - CAA AAA GGA GAC ACT TGT GAA CCC TGT GGC CG - #T GGG TTC TAC AAG         TCT     1043                                                                     Gln Lys Gly Asp Thr Cys Glu Pro Cys Gly Ar - #g Gly Phe Tyr Lys Ser                           275  - #               280  - #               285               - - TCC TCT CAA GAT CTT CAG TGC TCT CGT TGT CC - #A ACT CAC AGT TTT TCT          1091                                                                        Ser Ser Gln Asp Leu Gln Cys Ser Arg Cys Pr - #o Thr His Ser Phe Ser                        290      - #           295      - #           300                   - - GAT AAA GAA GGC TCC TCC AGA TGT GAA TGT GA - #A GAT GGG TAT TAC AGG          1139                                                                        Asp Lys Glu Gly Ser Ser Arg Cys Glu Cys Gl - #u Asp Gly Tyr Tyr Arg                    305          - #       310          - #       315                       - - GCT CCA TCT GAC CCA CCA TAC GTT GCA TGC AC - #A AGG CCT CCA TCT GCA          1187                                                                        Ala Pro Ser Asp Pro Pro Tyr Val Ala Cys Th - #r Arg Pro Pro Ser Ala                320              - #   325              - #   330                           - - CCA CAG AAC CTC ATT TTC AAC ATC AAC CAA AC - #C ACA GTA AGT TTG GAA          1235                                                                        Pro Gln Asn Leu Ile Phe Asn Ile Asn Gln Th - #r Thr Val Ser Leu Glu            335                 3 - #40                 3 - #45                 3 -       #50                                                                               - - TGG AGT CCT CCT GCA GAC AAT GGG GGA AGA AA - #C GAT GTG ACC TAC         AGA     1283                                                                     Trp Ser Pro Pro Ala Asp Asn Gly Gly Arg As - #n Asp Val Thr Tyr Arg                           355  - #               360  - #               365               - - ATA TTG TGT AAG CGG TGC AGT TGG GAG CAG GG - #C GAA TGT GTT CCC TGT          1331                                                                        Ile Leu Cys Lys Arg Cys Ser Trp Glu Gln Gl - #y Glu Cys Val Pro Cys                        370      - #           375      - #           380                   - - GGG AGT AAC ATT GGA TAC ATG CCC CAG CAG AC - #T GGA TTA GAG GAT AAC          1379                                                                        Gly Ser Asn Ile Gly Tyr Met Pro Gln Gln Th - #r Gly Leu Glu Asp Asn                    385          - #       390          - #       395                       - - TAT GTC ACT GTC ATG GAC CTG CTA GCC CAC GC - #T AAT TAT ACT TTT GAA          1427                                                                        Tyr Val Thr Val Met Asp Leu Leu Ala His Al - #a Asn Tyr Thr Phe Glu                400              - #   405              - #   410                           - - GTT GAA GCT GTA AAT GGA GTT TCT GAC TTA AG - #C CGA TCC CAG AGG CTC          1475                                                                        Val Glu Ala Val Asn Gly Val Ser Asp Leu Se - #r Arg Ser Gln Arg Leu            415                 4 - #20                 4 - #25                 4 -       #30                                                                               - - TTT GCT GCT GTC AGT ATC ACC ACT GGT CAA GC - #A GCT CCC TCG CAA         GTG     1523                                                                     Phe Ala Ala Val Ser Ile Thr Thr Gly Gln Al - #a Ala Pro Ser Gln Val                           435  - #               440  - #               445               - - AGC GGA GTA ATG AAG GAG AGA GTA CTG CAG CG - #G AGT GTC GAG CTT TCC          1571                                                                        Ser Gly Val Met Lys Glu Arg Val Leu Gln Ar - #g Ser Val Glu Leu Ser                        450      - #           455      - #           460                   - - TGG CAG GAA CCA GAG CAT CCC AAT GGA GTC AT - #C ACA GAA TAT GAA ATC          1619                                                                        Trp Gln Glu Pro Glu His Pro Asn Gly Val Il - #e Thr Glu Tyr Glu Ile                    465          - #       470          - #       475                       - - AAG TAT TAC GAG AAA GAT CAA AGG GAA CGG AC - #C TAC TCA ACA GTA AAA          1667                                                                        Lys Tyr Tyr Glu Lys Asp Gln Arg Glu Arg Th - #r Tyr Ser Thr Val Lys                480              - #   485              - #   490                           - - ACC AAG TCT ACT TCA GCC TCC ATT AAT AAT CT - #G AAA CCA GGA ACA GTG          1715                                                                        Thr Lys Ser Thr Ser Ala Ser Ile Asn Asn Le - #u Lys Pro Gly Thr Val            495                 5 - #00                 5 - #05                 5 -       #10                                                                               - - TAT GTT TTC CAG ATT CGG GCT TTT ACT GCT GC - #T GGT TAT GGA AAT         TAC     1763                                                                     Tyr Val Phe Gln Ile Arg Ala Phe Thr Ala Al - #a Gly Tyr Gly Asn Tyr                           515  - #               520  - #               525               - - AGT CCC AGA CTT GAT GTT GCT ACA CTA GAG GA - #A GCT ACA GGT AAA ATG          1811                                                                        Ser Pro Arg Leu Asp Val Ala Thr Leu Glu Gl - #u Ala Thr Gly Lys Met                        530      - #           535      - #           540                   - - TTT GAA GCT ACA GCT GTC TCC AGT GAA CAG AA - #T CCT GTT ATT ATC ATT          1859                                                                        Phe Glu Ala Thr Ala Val Ser Ser Glu Gln As - #n Pro Val Ile Ile Ile                    545          - #       550          - #       555                       - - GCT GTG GTT GCT GTA GCT GGG ACC ATC ATT TT - #G GTG TTC ATG GTC TTT          1907                                                                        Ala Val Val Ala Val Ala Gly Thr Ile Ile Le - #u Val Phe Met Val Phe                560              - #   565              - #   570                           - - GGC TTC ATC ATT GGG AGA AGG CAC TGT GGT TA - #T AGC AAA GCT GAC CAA          1955                                                                        Gly Phe Ile Ile Gly Arg Arg His Cys Gly Ty - #r Ser Lys Ala Asp Gln            575                 5 - #80                 5 - #85                 5 -       #90                                                                               - - GAA GGC GAT GAA GAG CTT TAC TTT CAT TTT AA - #A TTT CCA GGC ACC         AAA     2003                                                                     Glu Gly Asp Glu Glu Leu Tyr Phe His Phe Ly - #s Phe Pro Gly Thr Lys                           595  - #               600  - #               605               - - ACC TAC ATT GAC CCT GAA ACC TAT GAG GAC CC - #A AAT AGA GCT GTC CAT          2051                                                                        Thr Tyr Ile Asp Pro Glu Thr Tyr Glu Asp Pr - #o Asn Arg Ala Val His                        610      - #           615      - #           620                   - - CAA TTC GCC AAG GAG CTA GAT GCC TCC TGT AT - #T AAA ATT GAG CGT GTG          2099                                                                        Gln Phe Ala Lys Glu Leu Asp Ala Ser Cys Il - #e Lys Ile Glu Arg Val                    625          - #       630          - #       635                       - - ATT GGT GCA GGA GAA TTC GGT GAA GTC TGC AG - #T GGC CGT TTG AAA CTT          2147                                                                        Ile Gly Ala Gly Glu Phe Gly Glu Val Cys Se - #r Gly Arg Leu Lys Leu                640              - #   645              - #   650                           - - CCA GGG AAA AGA GAT GTT GCA GTA GCC ATA AA - #A ACC CTG AAA GTT GGT          2195                                                                        Pro Gly Lys Arg Asp Val Ala Val Ala Ile Ly - #s Thr Leu Lys Val Gly            655                 6 - #60                 6 - #65                 6 -       #70                                                                               - - TAC ACA GAA AAA CAA AGG AGA GAC TTT TTG TG - #T GAA GCA AGC ATC         ATG     2243                                                                     Tyr Thr Glu Lys Gln Arg Arg Asp Phe Leu Cy - #s Glu Ala Ser Ile Met                           675  - #               680  - #               685               - - GGG CAG TTT GAC CAC CCA AAT GTT GTC CAT TT - #G GAA GGG GTT GTT ACA          2291                                                                        Gly Gln Phe Asp His Pro Asn Val Val His Le - #u Glu Gly Val Val Thr                        690      - #           695      - #           700                   - - AGA GGG AAA CCA GTC ATG ATA GTA ATA GAG TT - #C ATG GAA AAT GGA GCC          2339                                                                        Arg Gly Lys Pro Val Met Ile Val Ile Glu Ph - #e Met Glu Asn Gly Ala                    705          - #       710          - #       715                       - - CTA GAT GCA TTT CTC AGG AAA CAT GAT GGG CA - #A TTT ACA GTC ATT CAG          2387                                                                        Leu Asp Ala Phe Leu Arg Lys His Asp Gly Gl - #n Phe Thr Val Ile Gln                720              - #   725              - #   730                           - - TTA GTA GGA ATG CTG AGA GGA ATT GCT GCT GG - #A ATG AGA TAT TTG GCT          2435                                                                        Leu Val Gly Met Leu Arg Gly Ile Ala Ala Gl - #y Met Arg Tyr Leu Ala            735                 7 - #40                 7 - #45                 7 -       #50                                                                               - - GAT ATG GGA TAT GTT CAC AGG GAC CTT GCA GC - #T CGC AAT ATT CTT         GTC     2483                                                                     Asp Met Gly Tyr Val His Arg Asp Leu Ala Al - #a Arg Asn Ile Leu Val                           755  - #               760  - #               765               - - AAC AGC AAT CTC GTT TGT AAA GTG TCA GAT TT - #T GGC CTG TCC CGA GTT          2531                                                                        Asn Ser Asn Leu Val Cys Lys Val Ser Asp Ph - #e Gly Leu Ser Arg Val                        770      - #           775      - #           780                   - - ATA GAG GAT GAT CCA GAA GCT GTC TAT ACA AC - #T ACT GGT GGA AAA ATT          2579                                                                        Ile Glu Asp Asp Pro Glu Ala Val Tyr Thr Th - #r Thr Gly Gly Lys Ile                    785          - #       790          - #       795                       - - CCA GTA AGG TGG ACA GCA CCC GAA GCC ATC CA - #G TAC CGG AAA TTC ACA          2627                                                                        Pro Val Arg Trp Thr Ala Pro Glu Ala Ile Gl - #n Tyr Arg Lys Phe Thr                800              - #   805              - #   810                           - - TCA GCC AGT GAT GTA TGG AGC TAT GGA ATA GT - #C ATG TGG GAA GTT ATG          2675                                                                        Ser Ala Ser Asp Val Trp Ser Tyr Gly Ile Va - #l Met Trp Glu Val Met            815                 8 - #20                 8 - #25                 8 -       #30                                                                               - - TCT TAT GGA GAA AGA CCT TAT TGG GAC ATG TC - #A AAT CAA GAT GTT         ATA     2723                                                                     Ser Tyr Gly Glu Arg Pro Tyr Trp Asp Met Se - #r Asn Gln Asp Val Ile                           835  - #               840  - #               845               - - AAA GCA ATA GAA GAA GGT TAT CGT TTA CCA GC - #A CCC ATG GAC TGC CCA          2771                                                                        Lys Ala Ile Glu Glu Gly Tyr Arg Leu Pro Al - #a Pro Met Asp Cys Pro                        850      - #           855      - #           860                   - - GCT GGC CTT CAC CAG CTA ATG TTG GAT TGT TG - #G CAA AAG GAG CGT GCT          2819                                                                        Ala Gly Leu His Gln Leu Met Leu Asp Cys Tr - #p Gln Lys Glu Arg Ala                    865          - #       870          - #       875                       - - GAA AGG CCA AAA TTT GAA CAG ATA GTT GGA AT - #T CTA GAC AAA ATG ATT          2867                                                                        Glu Arg Pro Lys Phe Glu Gln Ile Val Gly Il - #e Leu Asp Lys Met Ile                880              - #   885              - #   890                           - - CGA AAC CCA AAT AGT CTG AAA ACT CCC CTG GG - #A ACT TGT AGT AGG CCA          2915                                                                        Arg Asn Pro Asn Ser Leu Lys Thr Pro Leu Gl - #y Thr Cys Ser Arg Pro            895                 9 - #00                 9 - #05                 9 -       #10                                                                               - - ATA AGC CCT CTT CTG GAT CAA AAC ACT CCT GA - #T TTC ACT ACC TTT         TGT     2963                                                                     Ile Ser Pro Leu Leu Asp Gln Asn Thr Pro As - #p Phe Thr Thr Phe Cys                           915  - #               920  - #               925               - - TCA GTT GGA GAA TGG CTA CAA GCT ATT AAG AT - #G GAA AGA TAT AAA GAT          3011                                                                        Ser Val Gly Glu Trp Leu Gln Ala Ile Lys Me - #t Glu Arg Tyr Lys Asp                        930      - #           935      - #           940                   - - AAT TTC ACG GCA GCT GGC TAC AAT TCC CTT GA - #A TCA GTA GCC AGG ATG          3059                                                                        Asn Phe Thr Ala Ala Gly Tyr Asn Ser Leu Gl - #u Ser Val Ala Arg Met                    945          - #       950          - #       955                       - - ACT ATT GAG GAT GTG ATG AGT TTA GGG ATC AC - #A CTG GTT GGT CAT CAA          3107                                                                        Thr Ile Glu Asp Val Met Ser Leu Gly Ile Th - #r Leu Val Gly His Gln                960              - #   965              - #   970                           - - AAG AAA ATC ATG AGC AGC ATT CAG ACT ATG AG - #A GCA CAA ATG CTA CAT          3155                                                                        Lys Lys Ile Met Ser Ser Ile Gln Thr Met Ar - #g Ala Gln Met Leu His            975                 9 - #80                 9 - #85                 9 -       #90                                                                               - - TTA CAT GGA ACT GGC ATT CAA GTG TGA TATGCATTT - #C TCCCTTTTAA                3202                                                                       Leu His Gly Thr Gly Ile Gln Val  *                                                             995                                                             - - GGGAGATTAC AGACTGCAAG AGAACAGTAC TGGCCTTCAG TATATGCATA GA -              #ATGCTGCT   3262                                                                  - - AGAAGACAAG TGATGTCCTG GGTCCTTCCA ACAGTGAAGA GAAGATTTAA GA -             #AGCACCTA   3322                                                                  - - TAGACTTGAA CTCCTAAGTG CCACCAGAAT ATATAAAAAG GGAATTTAGG AT -             #CCACCATC   3382                                                                  - - GGTGGCCAGG AAAATAGCAG TGACAATAAA CAAAGTACTA CCTGAAAAAC AT -             #CCAAACAC   3442                                                                  - - CTTGAGCTCT CTAACCTCCT TTTTGTCTTA TAGACTTTTT AAAATGTACA TA -             #AAGAATTT   3502                                                                  - - AAGAAAGAAT ATATTTGTCA AATAAAATCA TGATCTTATT GTTAAAATTA AT -             #GAAATATT   3562                                                                  - - TTCCTTAAAT ATGTGATTTC AGACTATTCC TTTTTAAAAT CATTTGTGTT TA -             #TTCTTCAT   3622                                                                  - - AAGGACTTTG TTTTAGAAAG CTGTTTATAG CTTTGGACCT TTTTAGTGTT AA -             #ATCTGTAA   3682                                                                  - - CATTACTACA CTGGGTACCT TTGAAAGAAT CTCAAATTTC AAAAGAAATA GC -             #ATGATTGA   3742                                                                  - - AGATACATCT CTGTTAGAAC ATTGGTATCC TTTTTGTGCC ATTTTATTCT GT -             #TTAATCAG   3802                                                                  - - TGCTGTTTTG ATATTGTTTG CTAATTGGCA GGTAGTCAAG AAAATGCAAG TT -             #GCCAAGAG   3862                                                                  - - CTCTGATATT TTTTAAAAAG AATTTTTTTG TAAAGATCAG ACAACACACT AT -             #CTTTTCAA   3922                                                                  - - TGAAAAAAGC AATAATGATC CATACATACT ATAAGGCACT TTTAACAGAT TG -             #TTTATAGA   3982                                                                  - - GTGATTTTAC TAGAAAGAAT TTAATAAACT CGAAGTTTAG GTTTATGAGT AT -             #ATAAACAA   4042                                                                  - - ATGAGGCACT TCATCTGAAG AATGTTGGTG AAGGCAAGTC TCTGAAAGCA GA -             #ACTATCCA   4102                                                                  - - GTGTTATCTA AAAATTAATC TGAGCACATC AAGATTTTTT CATTCTCGTG AC -             #ATTAGGAA   4162                                                                  - - ATTTAGGATA AATAGTTGAC ATATATTTTA TATCCTCTTC TGTTGAATGC AG -             #TCCAAACA   4222                                                                  - - TGAAAGGAAA TAATTGTTTT ATATTATAAC TCTGAAGCAT GATAAAGGGG CA -             #GTTCACAA   4282                                                                  - - TTTTCACCAT TTAAACACAA ATTTGCTGCA CAGAATATCA CCATTGCAGT TC -             #AAAACAAA   4342                                                                  - - ACAAAACAAA AAGTCTTTTG TTTGTGAACA CTGATGCAAG AAACTTGTTA AA -             #TGAAAGGA   4402                                                                  - - CTCTTTACCC TAGAAGGAAG AGGTGAAGGA TCTGGCTTGT TTTTAAAGCT TT -             #ATTTATTA   4462                                                                  - - AACCATATTA TTTGATTACT GTGTTAGAAT TTCATAAGCA ATAATTAAAT GT -             #GTCTTTAT   4522                                                                  - - GGAATTC                 - #                  - #                        - #        4529                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:17:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  998 ami - #no acids                                               (B) TYPE: amino acid                                                           (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -           (xi) SEQUENCE DESCRIPTION: - # SEQ ID NO:17:                     - - Met Val Phe Gln Thr Arg Tyr Pro Ser Trp Il - #e Ile Leu Cys Tyr         Ile                                                                                1               5 - #                 10 - #                 15              - - Trp Leu Leu Arg Phe Ala His Thr Gly Glu Al - #a Gln Ala Ala Lys Glu                    20     - #             25     - #             30                   - - Val Leu Leu Leu Asp Ser Lys Ala Gln Gln Th - #r Glu Leu Glu Trp Ile                35         - #         40         - #         45                       - - Ser Ser Pro Pro Asn Gly Trp Glu Glu Ile Se - #r Gly Leu Asp Glu Asn            50             - #     55             - #     60                           - - Tyr Thr Pro Ile Arg Thr Tyr Gln Val Cys Gl - #n Val Met Glu Pro Asn        65                 - # 70                 - # 75                 - # 80        - - Gln Asn Asn Trp Leu Arg Thr Asn Trp Ile Se - #r Lys Gly Asn Ala Gln                        85 - #                 90 - #                 95               - - Arg Ile Phe Val Glu Leu Lys Phe Thr Leu Ar - #g Asp Cys Asn Ser Leu                   100      - #           105      - #           110                   - - Pro Gly Val Leu Gly Thr Cys Lys Glu Thr Ph - #e Asn Leu Tyr Tyr Tyr               115          - #       120          - #       125                       - - Glu Thr Asp Tyr Asp Thr Gly Arg Asn Ile Ar - #g Glu Asn Leu Tyr Val           130              - #   135              - #   140                           - - Lys Ile Asp Thr Ile Ala Ala Asp Glu Ser Ph - #e Thr Gln Gly Asp Leu       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Gly Glu Arg Lys Met Lys Leu Asn Thr Glu Va - #l Arg Glu Ile Gly         Pro                                                                                              165  - #               170  - #               175              - - Leu Ser Lys Lys Gly Phe Tyr Leu Ala Phe Gl - #n Asp Val Gly Ala Cys                   180      - #           185      - #           190                   - - Ile Ala Leu Val Ser Val Lys Val Tyr Tyr Ly - #s Lys Cys Trp Ser Ile               195          - #       200          - #       205                       - - Ile Glu Asn Leu Ala Ile Phe Pro Asp Thr Va - #l Thr Gly Ser Glu Phe           210              - #   215              - #   220                           - - Ser Ser Leu Val Glu Val Arg Gly Thr Cys Va - #l Ser Ser Ala Glu Glu       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Ala Glu Asn Ala Pro Arg Met His Cys Se - #r Ala Glu Gly Glu         Trp                                                                                              245  - #               250  - #               255              - - Leu Val Pro Ile Gly Lys Cys Ile Cys Lys Al - #a Gly Tyr Gln Gln Lys                   260      - #           265      - #           270                   - - Gly Asp Thr Cys Glu Pro Cys Gly Arg Gly Ph - #e Tyr Lys Ser Ser Ser               275          - #       280          - #       285                       - - Gln Asp Leu Gln Cys Ser Arg Cys Pro Thr Hi - #s Ser Phe Ser Asp Lys           290              - #   295              - #   300                           - - Glu Gly Ser Ser Arg Cys Glu Cys Glu Asp Gl - #y Tyr Tyr Arg Ala Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ser Asp Pro Pro Tyr Val Ala Cys Thr Arg Pr - #o Pro Ser Ala Pro         Gln                                                                                              325  - #               330  - #               335              - - Asn Leu Ile Phe Asn Ile Asn Gln Thr Thr Va - #l Ser Leu Glu Trp Ser                   340      - #           345      - #           350                   - - Pro Pro Ala Asp Asn Gly Gly Arg Asn Asp Va - #l Thr Tyr Arg Ile Leu               355          - #       360          - #       365                       - - Cys Lys Arg Cys Ser Trp Glu Gln Gly Glu Cy - #s Val Pro Cys Gly Ser           370              - #   375              - #   380                           - - Asn Ile Gly Tyr Met Pro Gln Gln Thr Gly Le - #u Glu Asp Asn Tyr Val       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Thr Val Met Asp Leu Leu Ala His Ala Asn Ty - #r Thr Phe Glu Val         Glu                                                                                              405  - #               410  - #               415              - - Ala Val Asn Gly Val Ser Asp Leu Ser Arg Se - #r Gln Arg Leu Phe Ala                   420      - #           425      - #           430                   - - Ala Val Ser Ile Thr Thr Gly Gln Ala Ala Pr - #o Ser Gln Val Ser Gly               435          - #       440          - #       445                       - - Val Met Lys Glu Arg Val Leu Gln Arg Ser Va - #l Glu Leu Ser Trp Gln           450              - #   455              - #   460                           - - Glu Pro Glu His Pro Asn Gly Val Ile Thr Gl - #u Tyr Glu Ile Lys Tyr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Tyr Glu Lys Asp Gln Arg Glu Arg Thr Tyr Se - #r Thr Val Lys Thr         Lys                                                                                              485  - #               490  - #               495              - - Ser Thr Ser Ala Ser Ile Asn Asn Leu Lys Pr - #o Gly Thr Val Tyr Val                   500      - #           505      - #           510                   - - Phe Gln Ile Arg Ala Phe Thr Ala Ala Gly Ty - #r Gly Asn Tyr Ser Pro               515          - #       520          - #       525                       - - Arg Leu Asp Val Ala Thr Leu Glu Glu Ala Th - #r Gly Lys Met Phe Glu           530              - #   535              - #   540                           - - Ala Thr Ala Val Ser Ser Glu Gln Asn Pro Va - #l Ile Ile Ile Ala Val       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Val Ala Val Ala Gly Thr Ile Ile Leu Val Ph - #e Met Val Phe Gly         Phe                                                                                              565  - #               570  - #               575              - - Ile Ile Gly Arg Arg His Cys Gly Tyr Ser Ly - #s Ala Asp Gln Glu Gly                   580      - #           585      - #           590                   - - Asp Glu Glu Leu Tyr Phe His Phe Lys Phe Pr - #o Gly Thr Lys Thr Tyr               595          - #       600          - #       605                       - - Ile Asp Pro Glu Thr Tyr Glu Asp Pro Asn Ar - #g Ala Val His Gln Phe           610              - #   615              - #   620                           - - Ala Lys Glu Leu Asp Ala Ser Cys Ile Lys Il - #e Glu Arg Val Ile Gly       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Ala Gly Glu Phe Gly Glu Val Cys Ser Gly Ar - #g Leu Lys Leu Pro         Gly                                                                                              645  - #               650  - #               655              - - Lys Arg Asp Val Ala Val Ala Ile Lys Thr Le - #u Lys Val Gly Tyr Thr                   660      - #           665      - #           670                   - - Glu Lys Gln Arg Arg Asp Phe Leu Cys Glu Al - #a Ser Ile Met Gly Gln               675          - #       680          - #       685                       - - Phe Asp His Pro Asn Val Val His Leu Glu Gl - #y Val Val Thr Arg Gly           690              - #   695              - #   700                           - - Lys Pro Val Met Ile Val Ile Glu Phe Met Gl - #u Asn Gly Ala Leu Asp       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Ala Phe Leu Arg Lys His Asp Gly Gln Phe Th - #r Val Ile Gln Leu         Val                                                                                              725  - #               730  - #               735              - - Gly Met Leu Arg Gly Ile Ala Ala Gly Met Ar - #g Tyr Leu Ala Asp Met                   740      - #           745      - #           750                   - - Gly Tyr Val His Arg Asp Leu Ala Ala Arg As - #n Ile Leu Val Asn Ser               755          - #       760          - #       765                       - - Asn Leu Val Cys Lys Val Ser Asp Phe Gly Le - #u Ser Arg Val Ile Glu           770              - #   775              - #   780                           - - Asp Asp Pro Glu Ala Val Tyr Thr Thr Thr Gl - #y Gly Lys Ile Pro Val       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Arg Trp Thr Ala Pro Glu Ala Ile Gln Tyr Ar - #g Lys Phe Thr Ser         Ala                                                                                              805  - #               810  - #               815              - - Ser Asp Val Trp Ser Tyr Gly Ile Val Met Tr - #p Glu Val Met Ser Tyr                   820      - #           825      - #           830                   - - Gly Glu Arg Pro Tyr Trp Asp Met Ser Asn Gl - #n Asp Val Ile Lys Ala               835          - #       840          - #       845                       - - Ile Glu Glu Gly Tyr Arg Leu Pro Ala Pro Me - #t Asp Cys Pro Ala Gly           850              - #   855              - #   860                           - - Leu His Gln Leu Met Leu Asp Cys Trp Gln Ly - #s Glu Arg Ala Glu Arg       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Pro Lys Phe Glu Gln Ile Val Gly Ile Leu As - #p Lys Met Ile Arg         Asn                                                                                              885  - #               890  - #               895              - - Pro Asn Ser Leu Lys Thr Pro Leu Gly Thr Cy - #s Ser Arg Pro Ile Ser                   900      - #           905      - #           910                   - - Pro Leu Leu Asp Gln Asn Thr Pro Asp Phe Th - #r Thr Phe Cys Ser Val               915          - #       920          - #       925                       - - Gly Glu Trp Leu Gln Ala Ile Lys Met Glu Ar - #g Tyr Lys Asp Asn Phe           930              - #   935              - #   940                           - - Thr Ala Ala Gly Tyr Asn Ser Leu Glu Ser Va - #l Ala Arg Met Thr Ile       945                 9 - #50                 9 - #55                 9 -       #60                                                                               - - Glu Asp Val Met Ser Leu Gly Ile Thr Leu Va - #l Gly His Gln Lys         Lys                                                                                              965  - #               970  - #               975              - - Ile Met Ser Ser Ile Gln Thr Met Arg Ala Gl - #n Met Leu His Leu His                   980      - #           985      - #           990                   - - Gly Thr Gly Ile Gln Val                                                           995                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:18:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 976 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:18:                        - -      Met Glu Leu Gln Ala Ala Arg Ala - # Cys Phe Ala Leu Leu Trp         Gly Cys                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Ala Leu Ala Ala Ala Ala Ala Ala - # Gln Gly Lys Glu Val Val        Leu Leu                                                                                           20 - #                 25 - #                 30              - -      Asp Phe Ala Ala Ala Gly Gly Glu - # Leu Gly Trp Leu Thr His         Pro Tyr                                                                                       35     - #             40     - #             45                   - -      Gly Lys Gly Trp Asp Leu Met Gln - # Asn Ile Met Asn Asp Met        Pro Ile                                                                                   50         - #         55         - #         60                       - -      Tyr Met Tyr Ser Val Cys Asn Val - # Met Ser Gly Asp Gln Asp        Asn Trp                                                                               65             - #     70             - #     75             - #          80                                                                             - -      Leu Arg Thr Asn Trp Val Tyr Arg - # Gly Glu Ala Glu Arg Asn         Asn Phe                                                                                            - #   85               - #   90               - #          95                                                                                - -      Glu Leu Asn Phe Thr Val Arg Asp - # Cys Asn Ser Phe Pro Gly        Gly Ala                                                                                           100 - #                105 - #                110             - -      Ser Ser Cys Lys Glu Thr Phe Asn - # Leu Tyr Tyr Ala Glu Ser         Asp Leu                                                                                       115     - #            120     - #            125                  - -      Asp Tyr Gly Thr Asn Phe Gln Lys - # Arg Leu Phe Thr Lys Ile        Asp Thr                                                                                   130         - #        135         - #        140                      - -      Ile Ala Pro Asp Glu Ile Thr Val - # Ser Ser Asp Phe Glu Ala        Arg His                                                                               145             - #    150             - #    155             - #         160                                                                            - -      Val Lys Leu Asn Val Glu Glu Arg - # Ser Val Gly Pro Leu Thr         Arg Lys                                                                                            - #   165              - #   170              - #          175                                                                               - -      Gly Phe Tyr Leu Ala Phe Gln Asp - # Ile Gly Ala Cys Val Ala        Leu Leu                                                                                           180 - #                185 - #                190             - -      Ser Val Arg Val Tyr Tyr Lys Lys - # Cys Pro Glu Leu Leu Gln         Gly Leu                                                                                       195     - #            200     - #            205                  - -      Ala His Phe Pro Glu Thr Ile Ala - # Gly Ser Asp Ala Pro Ser        Leu Ala                                                                                   210         - #        215         - #        220                      - -      Thr Val Ala Gly Thr Cys Val Asp - # His Ala Val Val Pro Pro        Gly Gly                                                                               225             - #    230             - #    235             - #         240                                                                            - -      Glu Glu Pro Arg Met His Cys Ala - # Val Asp Gly Glu Trp Leu         Val Pro                                                                                            - #   245              - #   250              - #          255                                                                               - -      Ile Gly Gln Cys Leu Cys Gln Ala - # Gly Tyr Glu Lys Val Glu        Asp Ala                                                                                           260 - #                265 - #                270             - -      Cys Gln Ala Cys Ser Pro Gly Phe - # Phe Lys Phe Glu Ala Ser         Glu Ser                                                                                       275     - #            280     - #            285                  - -      Pro Cys Leu Glu Cys Pro Glu His - # Thr Leu Pro Ser Pro Glu        Gly Ala                                                                                   290         - #        295         - #        300                      - -      Thr Ser Cys Glu Cys Glu Glu Gly - # Phe Phe Arg Ala Pro Gln        Asp Pro                                                                               305             - #    310             - #    315             - #         320                                                                            - -      Ala Ser Met Pro Cys Thr Arg Pro - # Pro Ser Ala Pro His Tyr         Leu Thr                                                                                            - #   325              - #   330              - #          335                                                                               - -      Ala Val Gly Met Gly Ala Lys Val - # Glu Leu Arg Trp Thr Pro        Pro Gln                                                                                           340 - #                345 - #                350             - -      Asp Ser Gly Gly Arg Glu Asp Ile - # Val Tyr Ser Val Thr Cys         Glu Gln                                                                                       355     - #            360     - #            365                  - -      Cys Trp Pro Glu Ser Gly Glu Cys - # Gly Pro Cys Glu Ala Ser        Val Arg                                                                                   370         - #        375         - #        380                      - -      Tyr Ser Glu Pro Pro His Gly Leu - # Thr Arg Thr Ser Val Thr        Val Ser                                                                               385             - #    390             - #    395             - #         400                                                                            - -      Asp Leu Glu Pro His Met Asn Tyr - # Thr Phe Thr Val Glu Ala         Arg Asn                                                                                            - #   405              - #   410              - #          415                                                                               - -      Gly Val Ser Gly Leu Val Thr Ser - # Arg Ser Phe Arg Thr Ala        Ser Val                                                                                           420 - #                425 - #                430             - -      Ser Ile Asn Gln Thr Glu Pro Pro - # Lys Val Arg Leu Glu Gly         Arg Ser                                                                                       435     - #            440     - #            445                  - -      Thr Thr Ser Leu Ser Val Ser Trp - # Ser Ile Pro Pro Pro Gln        Gln Ser                                                                                   450         - #        455         - #        460                      - -      Arg Val Trp Lys Tyr Glu Val Thr - # Tyr Arg Lys Lys Gly Asp        Ser Asn                                                                               465             - #    470             - #    475             - #         480                                                                            - -      Ser Tyr Asn Val Arg Arg Thr Glu - # Gly Phe Ser Val Thr Leu         Asp Asp                                                                                            - #   485              - #   490              - #          495                                                                               - -      Leu Ala Pro Asp Thr Thr Tyr Leu - # Val Gln Val Gln Ala Leu        Thr Gln                                                                                           500 - #                505 - #                510             - -      Glu Gly Gln Gly Ala Gly Ser Lys - # Val His Glu Phe Gln Thr         Leu Ser                                                                                       515     - #            520     - #            525                  - -      Pro Glu Gly Ser Gly Asn Leu Ala - # Val Ile Gly Gly Val Ala        Val Gly                                                                                   530         - #        535         - #        540                      - -      Val Val Leu Leu Leu Val Leu Ala - # Gly Val Gly Phe Phe Ile        His Arg                                                                               545             - #    550             - #    555             - #         560                                                                            - -      Arg Arg Lys Asn Gln Arg Ala Arg - # Gln Ser Pro Glu Asp Val         Tyr Phe                                                                                            - #   565              - #   570              - #          575                                                                               - -      Ser Lys Ser Glu Gln Leu Lys Pro - # Leu Lys Thr Tyr Val Asp        Pro His                                                                                           580 - #                585 - #                590             - -      Thr Tyr Glu Asp Pro Asn Gln Ala - # Val Leu Lys Phe Thr Thr         Glu Ile                                                                                       595     - #            600     - #            605                  - -      His Pro Ser Cys Val Thr Arg Gln - # Lys Val Ile Gly Ala Gly        Glu Phe                                                                                   610         - #        615         - #        620                      - -      Gly Glu Val Tyr Lys Gly Met Leu - # Lys Thr Ser Ser Gly Lys        Lys Glu                                                                               625             - #    630             - #    635             - #         640                                                                            - -      Val Pro Val Ala Ile Lys Thr Leu - # Lys Ala Gly Tyr Thr Glu         Lys Gln                                                                                            - #   645              - #   650              - #          655                                                                               - -      Arg Val Asp Phe Leu Gly Glu Ala - # Gly Ile Met Gly Gln Phe        Ser His                                                                                           660 - #                665 - #                670             - -      His Asn Ile Ile Arg Leu Glu Gly - # Val Ile Ser Lys Tyr Lys         Pro Met                                                                                       675     - #            680     - #            685                  - -      Met Ile Ile Thr Glu Tyr Met Glu - # Asn Gly Ala Leu Asp Lys        Phe Leu                                                                                   690         - #        695         - #        700                      - -      Arg Glu Lys Asp Gly Glu Phe Ser - # Val Leu Gln Leu Val Gly        Met Leu                                                                               705             - #    710             - #    715             - #         720                                                                            - -      Arg Gly Ile Ala Ala Gly Met Lys - # Tyr Leu Ala Asn Met Asn         Tyr Val                                                                                            - #   725              - #   730              - #          735                                                                               - -      His Arg Asp Leu Ala Ala Arg Asn - # Ile Leu Val Asn Ser Asn        Leu Val                                                                                           740 - #                745 - #                750             - -      Cys Lys Val Ser Asp Phe Gly Leu - # Ser Arg Val Leu Glu Asp         Asp Pro                                                                                       755     - #            760     - #            765                  - -      Glu Ala Thr Tyr Thr Thr Ser Gly - # Gly Lys Ile Pro Ile Arg        Trp Thr                                                                                   770         - #        775         - #        780                      - -      Ala Pro Glu Ala Ile Ser Tyr Arg - # Lys Phe Thr Ser Ala Ser        Asp Val                                                                               785             - #    790             - #    795             - #         800                                                                            - -      Trp Ser Phe Gly Ile Val Met Trp - # Glu Val Met Thr Tyr Gly         Glu Arg                                                                                            - #   805              - #   810              - #          815                                                                               - -      Pro Tyr Trp Glu Leu Ser Asn His - # Glu Val Met Lys Ala Ile        Asn Asp                                                                                           820 - #                825 - #                830             - -      Gly Phe Arg Leu Pro Thr Pro Met - # Asp Cys Pro Ser Ala Ile         Tyr Gln                                                                                       835     - #            840     - #            845                  - -      Leu Met Met Gln Cys Trp Gln Gln - # Glu Arg Ala Arg Arg Pro        Lys Phe                                                                                   850         - #        855         - #        860                      - -      Ala Asp Ile Val Ser Ile Leu Asp - # Lys Leu Ile Arg Ala Pro        Asp Ser                                                                               865             - #    870             - #    875             - #         880                                                                            - -      Leu Lys Thr Leu Ala Asp Phe Asp - # Pro Arg Val Ser Ile Arg         Leu Pro                                                                                            - #   885              - #   890              - #          895                                                                               - -      Ser Thr Ser Gly Ser Glu Gly Val - # Pro Phe Arg Thr Val Ser        Glu Trp                                                                                           900 - #                905 - #                910             - -      Leu Glu Ser Ile Lys Met Gln Gln - # Tyr Thr Glu His Phe Met         Ala Ala                                                                                       915     - #            920     - #            925                  - -      Gly Tyr Thr Ala Ile Glu Lys Val - # Val Gln Met Thr Asn Asp        Asp Ile                                                                                   930         - #        935         - #        940                      - -      Lys Arg Ile Gly Val Arg Leu Pro - # Gly His Gln Lys Arg Ile        Ala Tyr                                                                               945             - #    950             - #    955             - #         960                                                                            - -      Ser Leu Leu Gly Leu Lys Asp Gln - # Val Asn Thr Val Gly Ile         Pro Ile                                                                                            - #   965              - #   970              - #          975                                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:19:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 984 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:19:                        - -      Met Glu Arg Arg Trp Pro Leu Gly - # Leu Gly Leu Val Leu Leu        Leu Cys                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Ala Pro Leu Pro Pro Gly Ala Arg - # Ala Lys Glu Val Thr Leu        Met Asp                                                                                           20 - #                 25 - #                 30              - -      Thr Ser Lys Ala Gln Gly Glu Leu - # Gly Trp Leu Leu Asp Pro         Pro Lys                                                                                       35     - #             40     - #             45                   - -      Asp Gly Trp Ser Glu Gln Gln Gln - # Ile Leu Asn Gly Thr Pro        Leu Tyr                                                                                   50         - #         55         - #         60                       - -      Met Tyr Gln Asp Cys Pro Met Gln - # Gly Arg Arg Asp Thr Asp        His Trp                                                                               65             - #     70             - #     75             - #          80                                                                             - -      Leu Arg Ser Asn Trp Ile Tyr Arg - # Gly Glu Glu Ala Ser Arg         Val His                                                                                            - #   85               - #   90               - #          95                                                                                - -      Val Glu Leu Gln Phe Thr Val Arg - # Asp Cys Lys Ser Phe Pro        Gly Gly                                                                                           100 - #                105 - #                110             - -      Ala Gly Pro Leu Gly Cys Lys Glu - # Thr Phe Asn Leu Leu Tyr         Met Glu                                                                                       115     - #            120     - #            125                  - -      Ser Asp Gln Asp Val Gly Ile Gln - # Leu Arg Arg Pro Leu Phe        Gln Lys                                                                                   130         - #        135         - #        140                      - -      Val Thr Thr Val Ala Ala Asp Gln - # Ser Phe Thr Ile Arg Asp        Leu Ala                                                                               145             - #    150             - #    155             - #         160                                                                            - -      Ser Gly Ser Val Lys Leu Asn Val - # Glu Arg Cys Ser Leu Gly         Arg Leu                                                                                            - #   165              - #   170              - #          175                                                                               - -      Thr Arg Arg Gly Leu Tyr Leu Ala - # Phe His Asn Pro Gly Ala        Cys Val                                                                                           180 - #                185 - #                190             - -      Ala Leu Val Ser Val Arg Val Phe - # Tyr Gln Arg Cys Pro Glu         Thr Leu                                                                                       195     - #            200     - #            205                  - -      Asn Gly Leu Ala Gln Phe Pro Asp - # Thr Leu Pro Gly Pro Ala        Gly Leu                                                                                   210         - #        215         - #        220                      - -      Val Glu Val Ala Gly Thr Cys Leu - # Pro His Ala Arg Ala Ser        Pro Arg                                                                               225             - #    230             - #    235             - #         240                                                                            - -      Pro Ser Gly Ala Pro Arg Met His - # Cys Ser Pro Asp Gly Glu         Trp Leu                                                                                            - #   245              - #   250              - #          255                                                                               - -      Val Pro Val Gly Arg Cys His Cys - # Glu Pro Gly Tyr Glu Glu        Gly Gly                                                                                           260 - #                265 - #                270             - -      Ser Gly Glu Ala Cys Val Ala Cys - # Pro Ser Gly Ser Tyr Arg         Met Asp                                                                                       275     - #            280     - #            285                  - -      Met Asp Thr Pro His Cys Leu Thr - # Cys Pro Gln Gln Ser Thr        Ala Glu                                                                                   290         - #        295         - #        300                      - -      Ser Glu Gly Ala Thr Ile Cys Thr - # Cys Glu Ser Gly His Tyr        Arg Ala                                                                               305             - #    310             - #    315             - #         320                                                                            - -      Pro Gly Glu Gly Pro Gln Val Ala - # Cys Thr Gly Pro Pro Ser         Ala Pro                                                                                            - #   325              - #   330              - #          335                                                                               - -      Arg Asn Leu Ser Phe Ser Ala Ser - # Gly Thr Gln Leu Ser Leu        Arg Trp                                                                                           340 - #                345 - #                350             - -      Glu Pro Pro Ala Asp Thr Gly Gly - # Arg Gln Asp Val Arg Tyr         Ser Val                                                                                       355     - #            360     - #            365                  - -      Arg Cys Ser Gln Cys Gln Gly Thr - # Ala Gln Asp Gly Gly Pro        Cys Gln                                                                                   370         - #        375         - #        380                      - -      Pro Cys Gly Val Gly Val His Phe - # Ser Pro Gly Ala Arg Ala        Leu Thr                                                                               385             - #    390             - #    395             - #         400                                                                            - -      Thr Pro Ala Val His Val Asn Gly - # Leu Glu Pro Tyr Ala Asn         Tyr Thr                                                                                            - #   405              - #   410              - #          415                                                                               - -      Phe Asn Val Glu Ala Gln Asn Gly - # Val Ser Gly Leu Gly Ser        Ser Gly                                                                                           420 - #                425 - #                430             - -      His Ala Ser Thr Ser Val Ser Ile - # Ser Met Gly His Ala Glu         Ser Leu                                                                                       435     - #            440     - #            445                  - -      Ser Gly Leu Ser Leu Arg Leu Val - # Lys Lys Glu Pro Arg Gln        Leu Glu                                                                                   450         - #        455         - #        460                      - -      Leu Thr Trp Ala Gly Ser Arg Pro - # Arg Ser Pro Gly Ala Asn        Leu Thr                                                                               465             - #    470             - #    475             - #         480                                                                            - -      Tyr Glu Leu His Val Leu Asn Gln - # Asp Glu Glu Arg Tyr Gln         Met Val                                                                                            - #   485              - #   490              - #          495                                                                               - -      Leu Glu Pro Arg Val Leu Leu Thr - # Glu Leu Gln Pro Asp Thr        Thr Tyr                                                                                           500 - #                505 - #                510             - -      Ile Val Arg Val Arg Met Leu Thr - # Pro Leu Gly Pro Gly Pro         Phe Ser                                                                                       515     - #            520     - #            525                  - -      Pro Asp His Glu Phe Arg Thr Ser - # Pro Pro Val Ser Arg Gly        Leu Thr                                                                                   530         - #        535         - #        540                      - -      Gly Gly Glu Ile Val Ala Val Ile - # Phe Gly Leu Leu Leu Gly        Ala Ala                                                                               545             - #    550             - #    555             - #         560                                                                            - -      Leu Leu Leu Gly Ile Leu Val Phe - # Arg Ser Arg Arg Ala Gln         Arg Gln                                                                                            - #   565              - #   570              - #          575                                                                               - -      Arg Gln Gln Arg His Val Thr Ala - # Pro Pro Met Trp Ile Glu        Arg Thr                                                                                           580 - #                585 - #                590             - -      Ser Cys Ala Glu Ala Leu Cys Gly - # Thr Ser Arg His Thr Arg         Thr Leu                                                                                       595     - #            600     - #            605                  - -      His Arg Glu Pro Trp Thr Leu Pro - # Gly Gly Trp Ser Asn Phe        Pro Ser                                                                                   610         - #        615         - #        620                      - -      Arg Glu Leu Asp Pro Ala Trp Leu - # Met Val Asp Thr Val Ile        Gly Glu                                                                               625             - #    630             - #    635             - #         640                                                                            - -      Gly Glu Phe Gly Glu Val Tyr Arg - # Gly Thr Leu Arg Leu Pro         Ser Gln                                                                                            - #   645              - #   650              - #          655                                                                               - -      Asp Cys Lys Thr Val Ala Ile Lys - # Thr Leu Lys Asp Thr Ser        Pro Gly                                                                                           660 - #                665 - #                670             - -      Gly Gln Trp Trp Asn Phe Leu Arg - # Glu Ala Thr Ile Met Gly         Gln Phe                                                                                       675     - #            680     - #            685                  - -      Ser His Pro His Ile Leu His Leu - # Glu Gly Val Val Thr Lys        Arg Lys                                                                                   690         - #        695         - #        700                      - -      Pro Ile Met Ile Ile Thr Glu Phe - # Met Glu Asn Ala Ala Leu        Asp Ala                                                                               705             - #    710             - #    715             - #         720                                                                            - -      Phe Leu Arg Glu Arg Glu Asp Gln - # Leu Val Pro Gly Gln Leu         Val Ala                                                                                            - #   725              - #   730              - #          735                                                                               - -      Met Leu Gln Gly Ile Ala Ser Gly - # Met Asn Tyr Leu Ser Asn        His Asn                                                                                           740 - #                745 - #                750             - -      Tyr Val His Arg Asp Leu Ala Ala - # Arg Asn Ile Leu Val Asn         Gln Asn                                                                                       755     - #            760     - #            765                  - -      Leu Cys Cys Lys Val Ser Asp Phe - # Gly Leu Thr Arg Leu Leu        Asp Asp                                                                                   770         - #        775         - #        780                      - -      Phe Asp Gly Thr Tyr Glu Thr Gln - # Gly Gly Lys Ile Pro Ile        Arg Trp                                                                               785             - #    790             - #    795             - #         800                                                                            - -      Thr Ala Pro Glu Ala Ile Ala His - # Arg Ile Phe Thr Thr Ala         Ser Asp                                                                                            - #   805              - #   810              - #          815                                                                               - -      Val Trp Ser Phe Gly Ile Val Met - # Trp Glu Val Leu Ser Phe        Gly Asp                                                                                           820 - #                825 - #                830             - -      Lys Pro Tyr Gly Glu Met Ser Asn - # Gln Glu Val Met Lys Ser         Ile Glu                                                                                       835     - #            840     - #            845                  - -      Asp Gly Tyr Arg Leu Pro Pro Pro - # Val Asp Cys Pro Ala Pro        Leu Tyr                                                                                   850         - #        855         - #        860                      - -      Glu Leu Met Lys Asn Cys Trp Ala - # Tyr Asp Arg Ala Arg Arg        Pro His                                                                               865             - #    870             - #    875             - #         880                                                                            - -      Phe Gln Lys Leu Gln Ala His Leu - # Glu Gln Leu Leu Ala Asn         Pro His                                                                                            - #   885              - #   890              - #          895                                                                               - -      Ser Leu Arg Thr Ile Ala Asn Phe - # Asp Pro Arg Val Thr Leu        Arg Leu                                                                                           900 - #                905 - #                910             - -      Pro Ser Leu Ser Gly Ser Asp Gly - # Ile Pro Tyr Arg Thr Val         Ser Glu                                                                                       915     - #            920     - #            925                  - -      Trp Leu Glu Ser Ile Arg Met Lys - # Arg Tyr Ile Leu His Phe        His Ser                                                                                   930         - #        935         - #        940                      - -      Ala Gly Leu Asp Thr Met Glu Cys - # Val Leu Glu Leu Thr Ala        Glu Asp                                                                               945             - #    950             - #    955             - #         960                                                                            - -      Leu Thr Gln Met Gly Ile Thr Leu - # Pro Gly His Gln Lys Arg         Ile Leu                                                                                            - #   965              - #   970              - #          975                                                                               - -      Cys Ser Ile Gln Gly Phe Lys Asp                                                       980                                                            - -  - - (2) INFORMATION FOR SEQ ID NO:20:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 998 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:20:                        - -      Met Ala Arg Ala Arg Pro Pro Pro - # Pro Pro Ser Pro Pro Pro        Gly Leu                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Leu Pro Leu Leu Pro Pro Leu Leu - # Leu Leu Pro Leu Leu Leu        Leu Pro                                                                                           20 - #                 25 - #                 30              - -      Ala Gly Cys Arg Ala Leu Glu Glu - # Thr Leu Met Asp Thr Lys         Trp Val                                                                                       35     - #             40     - #             45                   - -      Thr Ser Glu Leu Ala Trp Thr Ser - # His Pro Glu Ser Gly Trp        Glu Glu                                                                                   50         - #         55         - #         60                       - -      Val Ser Gly Tyr Asp Glu Ala Met - # Asn Pro Ile Arg Thr Tyr        Gln Val                                                                               65             - #     70             - #     75             - #          80                                                                             - -      Cys Asn Val Arg Glu Ser Ser Gln - # Asn Asn Trp Leu Arg Thr         Gly Phe                                                                                            - #   85               - #   90               - #          95                                                                                - -      Ile Trp Arg Arg Asp Val Gln Arg - # Val Tyr Val Glu Leu Lys        Phe Thr                                                                                           100 - #                105 - #                110             - -      Val Arg Asp Cys Asn Ser Ile Pro - # Asn Ile Pro Gly Ser Cys         Lys Glu                                                                                       115     - #            120     - #            125                  - -      Thr Phe Asn Leu Phe Tyr Tyr Glu - # Ala Asp Ser Asp Val Ala        Ser Ala                                                                                   130         - #        135         - #        140                      - -      Ser Ser Pro Phe Trp Met Glu Asn - # Pro Tyr Val Lys Val Asp        Thr Ile                                                                               145             - #    150             - #    155             - #         160                                                                            - -      Ala Pro Asp Glu Ser Phe Ser Arg - # Leu Asp Ala Gly Arg Val         Asn Thr                                                                                            - #   165              - #   170              - #          175                                                                               - -      Lys Val Arg Ser Phe Gly Pro Leu - # Ser Lys Ala Gly Phe Tyr        Leu Ala                                                                                           180 - #                185 - #                190             - -      Phe Gln Asp Gln Gly Ala Cys Met - # Ser Leu Ile Ser Val Arg         Ala Phe                                                                                       195     - #            200     - #            205                  - -      Tyr Lys Lys Cys Ala Ser Thr Thr - # Ala Gly Phe Ala Leu Phe        Pro Glu                                                                                   210         - #        215         - #        220                      - -      Thr Leu Thr Gly Ala Glu Pro Thr - # Ser Leu Val Ile Ala Pro        Gly Thr                                                                               225             - #    230             - #    235             - #         240                                                                            - -      Cys Ile Pro Asn Ala Val Glu Val - # Ser Val Pro Leu Lys Leu         Tyr Cys                                                                                            - #   245              - #   250              - #          255                                                                               - -      Asn Gly Asp Gly Glu Trp Met Val - # Pro Val Gly Ala Cys Thr        Cys Ala                                                                                           260 - #                265 - #                270             - -      Thr Gly His Glu Pro Ala Ala Lys - # Glu Ser Gln Cys Arg Pro         Cys Pro                                                                                       275     - #            280     - #            285                  - -      Pro Gly Ser Tyr Lys Ala Lys Gln - # Gly Glu Gly Pro Cys Leu        Pro Cys                                                                                   290         - #        295         - #        300                      - -      Pro Pro Asn Ser Arg Thr Thr Ser - # Pro Ala Ala Ser Ile Cys        Thr Cys                                                                               305             - #    310             - #    315             - #         320                                                                            - -      His Asn Asn Phe Tyr Arg Ala Asp - # Ser Asp Ser Ala Asp Ser         Ala Cys                                                                                            - #   325              - #   330              - #          335                                                                               - -      Thr Thr Val Pro Ser Pro Pro Arg - # Gly Val Ile Ser Asn Val        Asn Glu                                                                                           340 - #                345 - #                350             - -      Thr Ser Leu Ile Leu Glu Trp Ser - # Glu Pro Arg Asp Leu Gly         Val Arg                                                                                       355     - #            360     - #            365                  - -      Asp Asp Leu Leu Tyr Asn Val Ile - # Cys Lys Lys Cys His Gly        Ala Gly                                                                                   370         - #        375         - #        380                      - -      Gly Ala Ser Ala Cys Ser Arg Cys - # Asp Asp Asn Val Glu Phe        Val Pro                                                                               385             - #    390             - #    395             - #         400                                                                            - -      Arg Gln Leu Gly Leu Ser Glu Pro - # Arg Val His Thr Ser His         Leu Leu                                                                                            - #   405              - #   410              - #          415                                                                               - -      Ala His Thr Arg Tyr Thr Phe Glu - # Val Gln Ala Val Asn Gly        Val Ser                                                                                           420 - #                425 - #                430             - -      Gly Lys Ser Pro Leu Pro Pro Arg - # Tyr Ala Ala Val Asn Ile         Thr Thr                                                                                       435     - #            440     - #            445                  - -      Asn Gln Ala Ala Pro Ser Glu Val - # Pro Thr Leu Arg Leu His        Ser Ser                                                                                   450         - #        455         - #        460                      - -      Ser Gly Ser Ser Leu Thr Leu Ser - # Trp Ala Pro Pro Glu Arg        Pro Asn                                                                               465             - #    470             - #    475             - #         480                                                                            - -      Gly Val Ile Leu Asp Tyr Glu Met - # Lys Tyr Phe Glu Lys Ser         Glu Gly                                                                                            - #   485              - #   490              - #          495                                                                               - -      Ile Ala Ser Thr Val Thr Ser Gln - # Met Asn Ser Val Gln Leu        Asp Gly                                                                                           500 - #                505 - #                510             - -      Leu Arg Pro Asp Ala Arg Tyr Val - # Val Gln Val Arg Ala Arg         Thr Val                                                                                       515     - #            520     - #            525                  - -      Ala Gly Tyr Gly Gln Tyr Ser Arg - # Pro Ala Glu Phe Glu Thr        Thr Ser                                                                                   530         - #        535         - #        540                      - -      Glu Arg Gly Ser Gly Ala Gln Gln - # Leu Gln Glu Gln Leu Pro        Leu Ile                                                                               545             - #    550             - #    555             - #         560                                                                            - -      Val Gly Ser Ala Thr Ala Gly Leu - # Val Phe Val Val Ala Val         Val Val                                                                                            - #   565              - #   570              - #          575                                                                               - -      Ile Ala Ile Val Cys Leu Arg Lys - # Gln Arg His Gly Ser Asp        Ser Glu                                                                                           580 - #                585 - #                590             - -      Tyr Thr Glu Lys Leu Gln Gln Tyr - # Ile Ala Pro Gly Met Lys         Val Tyr                                                                                       595     - #            600     - #            605                  - -      Ile Asp Pro Phe Thr Tyr Glu Asp - # Pro Asn Glu Ala Val Arg        Glu Phe                                                                                   610         - #        615         - #        620                      - -      Ala Lys Glu Ile Asp Val Ser Cys - # Val Lys Ile Glu Glu Val        Ile Gly                                                                               625             - #    630             - #    635             - #         640                                                                            - -      Ala Gly Glu Phe Gly Glu Val Cys - # Arg Gly Arg Leu Lys Gln         Pro Gly                                                                                            - #   645              - #   650              - #          655                                                                               - -      Arg Arg Glu Val Phe Val Ala Ile - # Lys Thr Leu Lys Val Gly        Tyr Thr                                                                                           660 - #                665 - #                670             - -      Glu Arg Gln Arg Arg Asp Phe Leu - # Ser Glu Ala Ser Ile Met         Gly Gln                                                                                       675     - #            680     - #            685                  - -      Phe Asp His Pro Asn Ile Ile Arg - # Leu Glu Gly Val Val Thr        Lys Ser                                                                                   690         - #        695         - #        700                      - -      Arg Pro Val Met Ile Leu Thr Glu - # Phe Met Glu Asn Cys Ala        Leu Asp                                                                               705             - #    710             - #    715             - #         720                                                                            - -      Ser Phe Leu Arg Leu Asn Asp Gly - # Gln Phe Thr Val Ile Gln         Leu Val                                                                                            - #   725              - #   730              - #          735                                                                               - -      Gly Met Leu Arg Gly Ile Ala Ala - # Gly Met Lys Tyr Leu Ser        Glu Met                                                                                           740 - #                745 - #                750             - -      Asn Tyr Val His Arg Asp Leu Ala - # Ala Arg Asn Ile Leu Val         Asn Ser                                                                                       755     - #            760     - #            765                  - -      Asn Leu Val Cys Lys Val Ser Asp - # Phe Gly Leu Ser Arg Phe        Leu Glu                                                                                   770         - #        775         - #        780                      - -      Asp Asp Pro Ser Asp Pro Thr Tyr - # Thr Ser Ser Leu Gly Gly        Lys Ile                                                                               785             - #    790             - #    795             - #         800                                                                            - -      Pro Ile Arg Trp Thr Ala Pro Glu - # Ala Ile Ala Tyr Arg Lys         Phe Thr                                                                                            - #   805              - #   810              - #          815                                                                               - -      Ser Ala Ser Asp Val Trp Ser Tyr - # Gly Ile Val Met Trp Glu        Val Met                                                                                           820 - #                825 - #                830             - -      Ser Tyr Gly Glu Arg Pro Tyr Trp - # Asp Met Ser Asn Gln Asp         Val Ile                                                                                       835     - #            840     - #            845                  - -      Asn Ala Val Glu Gln Asp Tyr Arg - # Leu Pro Pro Pro Met Asp        Cys Pro                                                                                   850         - #        855         - #        860                      - -      Thr Ala Leu His Gln Leu Met Leu - # Asp Cys Trp Val Arg Asp        Arg Asn                                                                               865             - #    870             - #    875             - #         880                                                                            - -      Leu Arg Pro Lys Phe Ser Gln Ile - # Val Asn Thr Leu Asp Lys         Leu Ile                                                                                            - #   885              - #   890              - #          895                                                                               - -      Arg Asn Ala Ala Ser Leu Lys Val - # Ile Ala Ser Ala Gln Ser        Gly Met                                                                                           900 - #                905 - #                910             - -      Ser Gln Pro Leu Leu Asp Arg Thr - # Val Pro Asp Tyr Thr Thr         Phe Thr                                                                                       915     - #            920     - #            925                  - -      Thr Val Gly Asp Trp Leu Asp Ala - # Ile Lys Met Gly Arg Tyr        Lys Glu                                                                                   930         - #        935         - #        940                      - -      Ser Phe Val Ser Ala Gly Phe Ala - # Ser Phe Asp Leu Val Ala        Gln Met                                                                               945             - #    950             - #    955             - #         960                                                                            - -      Thr Ala Glu Asp Leu Leu Arg Ile - # Gly Val Thr Leu Ala Gly         His Gln                                                                                            - #   965              - #   970              - #          975                                                                               - -      Lys Lys Ile Leu Ser Ser Ile Gln - # Asp Met Arg Leu Gln Met        Asn Gln                                                                                           980 - #                985 - #                990             - -      Thr Leu Pro Val Gln Val                                                           995                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:21:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 983 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:21:                        - -      Met Asp Cys Gln Leu Ser Ile Leu - # Leu Leu Leu Ser Cys Ser         Val Leu                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Asp Ser Phe Gly Glu Leu Ile Pro - # Gln Pro Ser Asn Glu Val        Asn Leu                                                                                           20 - #                 25 - #                 30              - -      Leu Asp Ser Lys Thr Ile Gln Gly - # Glu Leu Gly Trp Ile Ser         Tyr Pro                                                                                       35     - #             40     - #             45                   - -      Ser His Gly Trp Glu Glu Ile Ser - # Gly Val Asp Glu His Tyr        Thr Pro                                                                                   50         - #         55         - #         60                       - -      Ile Arg Thr Tyr Gln Val Cys Asn - # Val Met Asp His Ser Gln        Asn Asn                                                                               65             - #     70             - #     75             - #          80                                                                             - -      Trp Leu Arg Thr Asn Trp Val Pro - # Arg Asn Ser Ala Gln Lys         Ile Tyr                                                                                            - #   85               - #   90               - #          95                                                                                - -      Val Glu Leu Lys Phe Thr Leu Arg - # Asp Cys Asn Ser Ile Pro        Leu Val                                                                                           100 - #                105 - #                110             - -      Leu Gly Thr Cys Lys Glu Thr Phe - # Asn Leu Tyr Tyr Met Glu         Ser Asp                                                                                       115     - #            120     - #            125                  - -      Asp Asp His Gly Val Lys Phe Arg - # Glu His Gln Phe Thr Lys        Ile Asp                                                                                   130         - #        135         - #        140                      - -      Thr Ile Ala Ala Asp Glu Ser Phe - # Thr Gln Met Asp Leu Gly        Asp Arg                                                                               145             - #    150             - #    155             - #         160                                                                            - -      Ile Leu Lys Leu Asn Thr Glu Ile - # Arg Glu Val Gly Pro Val         Asn Lys                                                                                            - #   165              - #   170              - #          175                                                                               - -      Lys Gly Phe Tyr Leu Ala Phe Gln - # Asp Val Gly Ala Cys Val        Ala Leu                                                                                           180 - #                185 - #                190             - -      Val Ser Val Arg Val Tyr Phe Lys - # Lys Cys Pro Phe Thr Val         Lys Asn                                                                                       195     - #            200     - #            205                  - -      Leu Ala Met Phe Pro Asp Thr Val - # Pro Met Asp Ser Gln Ser        Leu Val                                                                                   210         - #        215         - #        220                      - -      Glu Val Arg Gly Ser Cys Val Asn - # Asn Ser Lys Glu Glu Asp        Pro Pro                                                                               225             - #    230             - #    235             - #         240                                                                            - -      Arg Met Tyr Cys Ser Thr Glu Gly - # Glu Trp Leu Val Pro Ile         Gly Lys                                                                                            - #   245              - #   250              - #          255                                                                               - -      Cys Ser Cys Asn Ala Gly Tyr Glu - # Glu Arg Gly Phe Met Cys        Gln Ala                                                                                           260 - #                265 - #                270             - -      Cys Arg Pro Gly Phe Tyr Lys Ala - # Leu Asp Gly Asn Met Lys         Cys Ala                                                                                       275     - #            280     - #            285                  - -      Lys Cys Pro Pro His Ser Ser Thr - # Gln Glu Asp Gly Ser Met        Asn Cys                                                                                   290         - #        295         - #        300                      - -      Arg Cys Glu Asn Asn Tyr Phe Arg - # Ala Asp Lys Asp Pro Pro        Ser Met                                                                               305             - #    310             - #    315             - #         320                                                                            - -      Ala Cys Thr Arg Pro Pro Ser Ser - # Pro Arg Asn Val Ile Ser         Asn Ile                                                                                            - #   325              - #   330              - #          335                                                                               - -      Asn Glu Thr Ser Val Ile Leu Asp - # Trp Ser Trp Pro Leu Asp        Thr Gly                                                                                           340 - #                345 - #                350             - -      Gly Arg Lys Asp Val Thr Phe Asn - # Ile Ile Cys Lys Lys Cys         Gly Trp                                                                                       355     - #            360     - #            365                  - -      Asn Ile Lys Gln Cys Glu Pro Cys - # Ser Pro Asn Val Arg Phe        Leu Pro                                                                                   370         - #        375         - #        380                      - -      Arg Gln Phe Gly Leu Thr Asn Thr - # Thr Val Thr Val Thr Asp        Leu Leu                                                                               385             - #    390             - #    395             - #         400                                                                            - -      Ala His Thr Asn Tyr Thr Phe Glu - # Ile Asp Ala Val Asn Gly         Val Ser                                                                                            - #   405              - #   410              - #          415                                                                               - -      Glu Leu Ser Ser Pro Pro Arg Gln - # Phe Ala Ala Val Ser Ile        Thr Thr                                                                                           420 - #                425 - #                430             - -      Asn Gln Ala Ala Pro Ser Pro Val - # Leu Thr Ile Lys Lys Asp         Arg Thr                                                                                       435     - #            440     - #            445                  - -      Ser Arg Asn Ser Ile Ser Leu Ser - # Trp Gln Glu Pro Glu His        Pro Asn                                                                                   450         - #        455         - #        460                      - -      Gly Ile Ile Leu Asp Tyr Glu Val - # Lys Tyr Tyr Glu Lys Gln        Glu Gln                                                                               465             - #    470             - #    475             - #         480                                                                            - -      Glu Thr Ser Tyr Thr Ile Leu Arg - # Ala Arg Gly Thr Asn Val         Thr Ile                                                                                            - #   485              - #   490              - #          495                                                                               - -      Ser Ser Leu Lys Pro Asp Thr Ile - # Tyr Val Leu Gln Ile Arg        Ala Arg                                                                                           500 - #                505 - #                510             - -      Thr Ala Ala Gly Tyr Gly Thr Asn - # Ser Arg Lys Phe Glu Phe         Glu Thr                                                                                       515     - #            520     - #            525                  - -      Ser Pro Asp Ser Phe Ser Ile Ser - # Gly Glu Ser Ser Gln Val        Val Met                                                                                   530         - #        535         - #        540                      - -      Ile Ala Ile Ser Ala Ala Val Ala - # Ile Ile Leu Leu Thr Val        Val Ile                                                                               545             - #    550             - #    555             - #         560                                                                            - -      Tyr Val Leu Ile Gly Arg Phe Cys - # Gly Tyr Lys Ser Lys His         Gly Ala                                                                                            - #   565              - #   570              - #          575                                                                               - -      Asp Glu Lys Arg Leu His Phe Gly - # Asn Gly His Leu Lys Leu        Pro Gly                                                                                           580 - #                585 - #                590             - -      Leu Arg Thr Tyr Val Asp Pro His - # Thr Tyr Glu Asp Pro Thr         Gln Ala                                                                                       595     - #            600     - #            605                  - -      Val His Glu Phe Ala Lys Glu Leu - # Asp Ala Thr Asn Ile Ser        Ile Asp                                                                                   610         - #        615         - #        620                      - -      Lys Val Val Gly Ala Gly Glu Phe - # Gly Glu Val Cys Ser Gly        Arg Leu                                                                               625             - #    630             - #    635             - #         640                                                                            - -      Lys Leu Pro Ser Lys Lys Glu Ile - # Ser Val Ala Ile Lys Thr         Leu Lys                                                                                            - #   645              - #   650              - #          655                                                                               - -      Val Gly Tyr Thr Glu Lys Gln Arg - # Arg Asp Phe Leu Gly Glu        Ala Ser                                                                                           660 - #                665 - #                670             - -      Ile Met Gly Gln Phe Asp His Pro - # Asn Ile Ile Arg Leu Glu         Gly Val                                                                                       675     - #            680     - #            685                  - -      Val Thr Lys Ser Lys Pro Val Met - # Ile Val Thr Glu Tyr Met        Glu Asn                                                                                   690         - #        695         - #        700                      - -      Gly Ser Leu Asp Ser Phe Leu Arg - # Lys His Asp Ala Gln Phe        Thr Val                                                                               705             - #    710             - #    715             - #         720                                                                            - -      Ile Gln Leu Val Gly Met Leu Arg - # Gly Ile Ala Ser Gly Met         Lys Tyr                                                                                            - #   725              - #   730              - #          735                                                                               - -      Leu Ser Asp Met Gly Tyr Val His - # Arg Asp Leu Ala Ala Arg        Asn Ile                                                                                           740 - #                745 - #                750             - -      Leu Ile Asn Ser Asn Leu Val Cys - # Lys Val Ser Asp Phe Gly         Leu Ser                                                                                       755     - #            760     - #            765                  - -      Arg Val Leu Glu Asp Asp Pro Glu - # Ala Ala Tyr Thr Thr Arg        Gly Gly                                                                                   770         - #        775         - #        780                      - -      Lys Ile Pro Ile Arg Trp Thr Ser - # Pro Glu Ala Ile Ala Tyr        Arg Lys                                                                               785             - #    790             - #    795             - #         800                                                                            - -      Phe Thr Ser Ala Ser Asp Val Trp - # Ser Tyr Gly Ile Val Leu         Trp Glu                                                                                            - #   805              - #   810              - #          815                                                                               - -      Val Met Ser Tyr Gly Glu Arg Pro - # Tyr Trp Glu Met Ser Asn        Gln Asp                                                                                           820 - #                825 - #                830             - -      Val Ile Lys Ala Val Asp Glu Gly - # Tyr Arg Leu Pro Pro Pro         Met Asp                                                                                       835     - #            840     - #            845                  - -      Cys Pro Ala Ala Leu Tyr Gln Leu - # Met Leu Asp Cys Trp Gln        Lys Asp                                                                                   850         - #        855         - #        860                      - -      Arg Asn Asn Arg Pro Lys Phe Glu - # Gln Ile Val Ser Ile Leu        Asp Lys                                                                               865             - #    870             - #    875             - #         880                                                                            - -      Leu Ile Arg Asn Pro Gly Ser Leu - # Lys Ile Ile Thr Ser Ala         Ala Ala                                                                                            - #   885              - #   890              - #          895                                                                               - -      Arg Pro Ser Asn Leu Leu Leu Asp - # Gln Ser Asn Val Asp Ile        Ser Thr                                                                                           900 - #                905 - #                910             - -      Phe Arg Thr Thr Gly Asp Trp Leu - # Asn Gly Val Arg Thr Ala         His Cys                                                                                       915     - #            920     - #            925                  - -      Lys Glu Ile Phe Thr Gly Val Glu - # Tyr Ser Ser Cys Asp Thr        Ile Ala                                                                                   930         - #        935         - #        940                      - -      Lys Ile Ser Thr Asp Asp Met Lys - # Lys Val Gly Val Thr Val        Val Gly                                                                               945             - #    950             - #    955             - #         960                                                                            - -      Pro Gln Lys Lys Ile Ile Ser Ser - # Ile Lys Ala Leu Glu Thr         Gln Ser                                                                                            - #   965              - #   970              - #          975                                                                               - -      Lys Asn Gly Pro Val Pro Val                                                           980                                                            - -  - - (2) INFORMATION FOR SEQ ID NO:22:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 24 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:22:                        - - CTGCTCGCCG CCGTGGAAGA AACG          - #                  - #                     24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:23:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 39 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:23:                        - - GCGTCTAGAT TATCACTTCT CCTGGATGCT TGTCTGGTA      - #                       - #    39                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:24:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 48 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:24:                        - - GCGGACGCCG CCGCCATGGC CCTGGATTGC CTGCTGCTGT TCCTCCTG  - #                     48                                                                          - -  - - (2) INFORMATION FOR SEQ ID NO:25:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 54 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:25:                        - - CGTTTCTTCC ACGGCGGCGA GCAGAGATGC CAGGAGGAAC AGCAGCAGGC AA - #TC                54                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:26:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 13 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:26:                        - -      Met Ala Leu Asp Cys Leu Leu Leu - # Phe Leu Leu Ala Ser                   1             - #  5                - #   10                               - -  - - (2) INFORMATION FOR SEQ ID NO:27:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 26 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:27:                        - - AGGGAATTCC AYCGNGAYYT NGCNGC          - #                  - #                   26                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:28:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 24 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:28:                        - - AGGGGATCCR WARSWCCANA CRTC          - #                  - #                     24                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:29:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 687 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:29:                        - -      Met Ala Arg Ala Arg Pro Pro Ser - # Leu Leu Leu Leu Leu Leu         Asp Ala                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Leu Ala Ala Pro Ala Glu Val Thr - # Leu Leu Asp Ser Lys Thr        Gln Gly                                                                                           20 - #                 25 - #                 30              - -      Glu Leu Gly Trp Ile Ser His Pro - # Pro Gly Trp Glu Glu Ser         Gly Asp                                                                                       35     - #             40     - #             45                   - -      Glu Asn Thr Pro Ile Arg Thr Tyr - # Gln Val Cys Asn Val Met        Glu Ser                                                                                   50         - #         55         - #         60                       - -      Gln Asn Asn Trp Leu Arg Thr Asn - # Trp Ile Ala Phe Gln Asp        Val Gly                                                                               65             - #     70             - #     75             - #          80                                                                             - -      Ala Cys Ala Leu Val Ser Val Arg - # Val Tyr Lys Lys Cys Pro         Ser Thr                                                                                            - #   85               - #   90               - #          95                                                                                - -      Val Asn Leu Ala Phe Pro Asp Thr - # Thr Gly Ala Asp Ser Ser        Ser Leu                                                                                           100 - #                105 - #                110             - -      Val Glu Val Arg Gly Cys Val Asn - # Asn Ala Glu Pro Pro Met         Cys Ser                                                                                       115     - #            120     - #            125                  - -      Ala Asp Gly Glu Trp Leu Val Pro - # Ile Gly Lys Cys Cys Lys        Ala Gly                                                                                   130         - #        135         - #        140                      - -      Tyr Glu Glu Gly Thr Ala Cys Gln - # Ala Cys Pro Cys Glu Pro        Cys Gly                                                                               145             - #    150             - #    155             - #         160                                                                            - -      Asn Val Arg Tyr Pro Arg Gln Leu - # Gly Leu Thr Thr Val Thr         Val Ser                                                                                            - #   165              - #   170              - #          175                                                                               - -      Asp Leu Leu Ala His Thr Asn Tyr - # Thr Phe Glu Glu Ala Val        Asn Gly                                                                                           180 - #                185 - #                190             - -      Val Ser Leu Ser Pro Gln Ala Ser - # Val Ser Val Ile Thr Thr         Asn Gln                                                                                       195     - #            200     - #            205                  - -      Ala Ala Pro Ser Val Thr Val Arg - # Ser Arg Ser Ser Leu Ser        Trp Gln                                                                                   210         - #        215         - #        220                      - -      Glu Pro Arg Pro Asn Gly Val Ile - # Leu Tyr Glu Val Lys Tyr        Tyr Glu                                                                               225             - #    230             - #    235             - #         240                                                                            - -      Lys Asp Gln Glu Arg Ser Tyr Ile - # Val Lys Thr Ser Val Thr         Asp Gly                                                                                            - #   245              - #   250              - #          255                                                                               - -      Leu Lys Pro Asp Thr Tyr Val Phe - # Gln Val Arg Ala Arg Thr        Ala Ala                                                                                           260 - #                265 - #                270             - -      Gly Tyr Gly Ser Arg Glu Phe Glu - # Thr Pro Glu Ala Ser Gly         Ser Gly                                                                                       275     - #            280     - #            285                  - -      Ile Val Val Val Ile Ile Val Ser - # Ala Gly Ala Leu Leu Val        Val Val                                                                                   290         - #        295         - #        300                      - -      Leu Arg Arg Gln Ser Arg Asp Asp - # Glu Tyr Lys Glu Gln Lys        Leu Pro                                                                               305             - #    310             - #    315             - #         320                                                                            - -      Gly Lys Thr Tyr Ile Asp Pro Thr - # Tyr Glu Asp Pro Asn Gln         Ala Val                                                                                            - #   325              - #   330              - #          335                                                                               - -      Glu Phe Ala Lys Glu Ile Asp Ala - # Ser Cys Ile Lys Ile Glu        Lys Val                                                                                           340 - #                345 - #                350             - -      Ile Gly Ala Gly Glu Phe Gly Glu - # Val Cys Ser Gly Arg Leu         Lys Leu                                                                                       355     - #            360     - #            365                  - -      Pro Gly Lys Arg Glu Val Ala Ile - # Lys Thr Leu Lys Val Gly        Tyr Thr                                                                                   370         - #        375         - #        380                      - -      Glu Lys Gln Arg Arg Asp Phe Leu - # Glu Ala Ser Ile Met Gly        Gln Phe                                                                               385             - #    390             - #    395             - #         400                                                                            - -      Asp His Pro Asn Ile Ile His Leu - # Glu Gly Val Val Thr Lys         Ser Lys                                                                                            - #   405              - #   410              - #          415                                                                               - -      Pro Val Met Ile Ile Thr Glu Met - # Glu Asn Gly Leu Asp Phe        Leu Arg                                                                                           420 - #                425 - #                430             - -      Lys Asn Asp Gly Gln Phe Thr Val - # Ile Gln Leu Val Gly Met         Leu Arg                                                                                       435     - #            440     - #            445                  - -      Gly Ile Ala Ala Gly Met Lys Tyr - # Leu Ser Asp Met Asn Tyr        Val His                                                                                   450         - #        455         - #        460                      - -      Arg Asp Leu Ala Ala Arg Asn Ile - # Leu Val Asn Ser Asn Leu        Val Cys                                                                               465             - #    470             - #    475             - #         480                                                                            - -      Lys Val Ser Asp Phe Gly Leu Ser - # Arg Val Leu Glu Asp Asp         Pro Glu                                                                                            - #   485              - #   490              - #          495                                                                               - -      Ala Tyr Thr Thr Arg Gly Gly Lys - # Ile Pro Ile Arg Trp Thr        Ala Pro                                                                                           500 - #                505 - #                510             - -      Glu Ala Ile Ala Tyr Arg Lys Phe - # Thr Ser Ala Ser Asp Val         Trp Ser                                                                                       515     - #            520     - #            525                  - -      Tyr Gly Ile Val Met Trp Glu Val - # Met Ser Tyr Gly Glu Arg        Pro Tyr                                                                                   530         - #        535         - #        540                      - -      Trp Met Ser Asn Gln Asp Val Ile - # Lys Ala Ile Glu Glu Gly        Tyr Arg                                                                               545             - #    550             - #    555             - #         560                                                                            - -      Leu Pro Pro Pro Met Asp Cys Pro - # Ala Ala Leu Gln Leu Met         Leu Asp                                                                                            - #   565              - #   570              - #          575                                                                               - -      Cys Trp Gln Lys Arg Asn Arg Arg - # Pro Lys Phe Gln Ile Val        Asn Ile                                                                                           580 - #                585 - #                590             - -      Leu Asp Lys Leu Ile Arg Asn Pro - # Asn Ser Leu Lys Thr Ile         Ala Ala                                                                                       595     - #            600     - #            605                  - -      Ser Ser Arg Ser Pro Leu Leu Asp - # Ser Gly Pro Asp Thr Thr        Phe Arg                                                                                   610         - #        615         - #        620                      - -      Thr Val Gly Glu Trp Leu Glu Ala - # Ile Lys Met Gly Arg Tyr        Lys Glu                                                                               625             - #    630             - #    635             - #         640                                                                            - -      Phe Thr Ala Ala Gly Tyr Thr Ser - # Ala Val Ala Gln Met Thr         Ala Glu                                                                                            - #   645              - #   650              - #          655                                                                               - -      Asp Leu Arg Ile Gly Val Thr Leu - # Val Gly His Gln Lys Lys        Ile Leu                                                                                           660 - #                665 - #                670             - -      Ser Ser Ile Gln Met Arg Gln Met - # Asn Gln Gly His Pro Val         Val                                                                                           675     - #            680     - #            685                  - -  - - (2) INFORMATION FOR SEQ ID NO:30:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 967 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:30:                        - -      Ala Leu Arg Thr Leu Leu Ala Ser - # Pro Ser Asn Glu Val Asn        Leu Leu                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Asp Ser Arg Thr Val Met Gly Asp - # Leu Gly Trp Ile Ala Phe        Pro Lys                                                                                           20 - #                 25 - #                 30              - -      Asn Gly Trp Glu Glu Ile Gly Glu - # Val Asp Glu Asn Tyr Ala         Pro Ile                                                                                       35     - #             40     - #             45                   - -      His Thr Tyr Gln Val Cys Lys Val - # Met Glu Gln Asn Gln Asn        Asn Trp                                                                                   50         - #         55         - #         60                       - -      Leu Leu Thr Ser Trp Ile Ser Asn - # Glu Gly Ala Ser Arg Ile        Phe Ile                                                                               65             - #     70             - #     75             - #          80                                                                             - -      Glu Leu Lys Phe Thr Leu Arg Asp - # Cys Asn Ser Leu Pro Gly         Gly Leu                                                                                            - #   85               - #   90               - #          95                                                                                - -      Gly Thr Cys Lys Glu Thr Phe Asn - # Met Tyr Tyr Phe Glu Ser        Asp Asp                                                                                           100 - #                105 - #                110             - -      Gln Asn Gly Arg Asn Ile Lys Glu - # Asn Gln Tyr Ile Lys Ile         Asp Thr                                                                                       115     - #            120     - #            125                  - -      Ile Ala Ala Asp Glu Ser Phe Thr - # Glu Leu Asp Leu Gly Asp        Arg Val                                                                                   130         - #        135         - #        140                      - -      Met Lys Leu Asn Thr Glu Val Arg - # Asp Val Gly Pro Leu Ser        Lys Lys                                                                               145             - #    150             - #    155             - #         160                                                                            - -      Gly Phe Tyr Leu Ala Phe Gln Asp - # Val Gly Ala Cys Ile Ala         Leu Val                                                                                            - #   165              - #   170              - #          175                                                                               - -      Ser Val Arg Val Tyr Tyr Lys Lys - # Cys Pro Ser Val Val Arg        His Leu                                                                                           180 - #                185 - #                190             - -      Ala Val Phe Pro Asp Thr Ile Thr - # Gly Ala Asp Ser Ser Gln         Leu Leu                                                                                       195     - #            200     - #            205                  - -      Glu Val Ser Gly Ser Cys Val Asn - # His Ser Val Thr Asp Glu        Pro Pro                                                                                   210         - #        215         - #        220                      - -      Lys Met His Cys Ser Ala Glu Gly - # Glu Trp Leu Val Pro Ile        Gly Lys                                                                               225             - #    230             - #    235             - #         240                                                                            - -      Cys Met Cys Lys Ala Gly Tyr Glu - # Glu Lys Asn Gly Thr Cys         Gln Val                                                                                            - #   245              - #   250              - #          255                                                                               - -      Cys Arg Pro Gly Phe Phe Lys Ala - # Ser Pro His Ile Gln Ser        Cys Gly                                                                                           260 - #                265 - #                270             - -      Lys Cys Pro Pro His Ser Tyr Thr - # His Glu Glu Ala Ser Thr         Ser Cys                                                                                       275     - #            280     - #            285                  - -      Val Cys Glu Lys Asp Tyr Phe Arg - # Arg Glu Ser Asp Pro Pro        Thr Met                                                                                   290         - #        295         - #        300                      - -      Ala Cys Thr Arg Pro Pro Ser Ala - # Pro Arg Asn Ala Ile Ser        Asn Val                                                                               305             - #    310             - #    315             - #         320                                                                            - -      Asn Glu Thr Ser Val Phe Leu Glu - # Trp Ile Pro Pro Ala Asp         Thr Gly                                                                                            - #   325              - #   330              - #          335                                                                               - -      Gly Arg Lys Asp Val Ser Tyr Tyr - # Ile Ala Cys Lys Lys Cys        Asn Ser                                                                                           340 - #                345 - #                350             - -      His Ala Gly Val Cys Glu Glu Cys - # Gly Gly His Val Arg Tyr         Leu Pro                                                                                       355     - #            360     - #            365                  - -      Arg Gln Ser Gly Leu Lys Asn Thr - # Ser Val Met Met Val Asp        Leu Leu                                                                                   370         - #        375         - #        380                      - -      Ala His Thr Asn Tyr Thr Phe Glu - # Ile Glu Ala Val Asn Gly        Val Ser                                                                               385             - #    390             - #    395             - #         400                                                                            - -      Asp Leu Ser Pro Gly Ala Arg Gln - # Tyr Val Ser Val Asn Val         Thr Thr                                                                                            - #   405              - #   410              - #          415                                                                               - -      Asn Gln Ala Ala Pro Ser Pro Val - # Thr Asn Val Lys Lys Gly        Lys Ile                                                                                           420 - #                425 - #                430             - -      Ala Lys Asn Ser Ile Ser Leu Ser - # Trp Gln Glu Pro Asp Arg         Pro Asn                                                                                       435     - #            440     - #            445                  - -      Gly Ile Ile Leu Glu Tyr Glu Ile - # Lys His Phe Glu Lys Asp        Gln Glu                                                                                   450         - #        455         - #        460                      - -      Thr Ser Tyr Thr Ile Ile Lys Ser - # Lys Glu Thr Thr Ile Thr        Ala Glu                                                                               465             - #    470             - #    475             - #         480                                                                            - -      Gly Leu Lys Pro Ala Ser Val Tyr - # Val Phe Gln Ile Arg Ala         Arg Thr                                                                                            - #   485              - #   490              - #          495                                                                               - -      Ala Ala Gly Tyr Gly Val Phe Ser - # Arg Arg Phe Glu Phe Glu        Thr Thr                                                                                           500 - #                505 - #                510             - -      Pro Val Phe Ala Ala Ser Ser Asp - # Gln Ser Gln Ile Pro Val         Ile Ala                                                                                       515     - #            520     - #            525                  - -      Val Ser Val Thr Val Gly Val Ile - # Leu Leu Ala Val Val Ile        Gly Val                                                                                   530         - #        535         - #        540                      - -      Leu Leu Ser Gly Arg Arg Cys Gly - # Tyr Ser Lys Ala Lys Gln        Asp Pro                                                                               545             - #    550             - #    555             - #         560                                                                            - -      Glu Glu Glu Lys Met His Phe His - # Asn Gly His Ile Lys Leu         Pro Gly                                                                                            - #   565              - #   570              - #          575                                                                               - -      Val Arg Thr Tyr Ile Asp Pro His - # Thr Tyr Glu Asp Pro Asn        Gln Ala                                                                                           580 - #                585 - #                590             - -      Val His Glu Phe Ala Lys Glu Ile - # Glu Ala Ser Cys Ile Thr         Ile Glu                                                                                       595     - #            600     - #            605                  - -      Arg Val Ile Gly Ala Gly Glu Phe - # Gly Glu Val Cys Ser Gly        Arg Leu                                                                                   610         - #        615         - #        620                      - -      Lys Leu Pro Gly Lys Arg Glu Leu - # Pro Val Ala Ile Lys Thr        Leu Lys                                                                               625             - #    630             - #    635             - #         640                                                                            - -      Val Gly Tyr Thr Glu Lys Gln Arg - # Arg Asp Phe Leu Gly Glu         Ala Ser                                                                                            - #   645              - #   650              - #          655                                                                               - -      Ile Met Gly Gln Phe Asp His Pro - # Asn Ile Ile His Leu Glu        Gly Val                                                                                           660 - #                665 - #                670             - -      Val Thr Lys Ser Lys Pro Val Met - # Ile Val Thr Glu Tyr Met         Glu Asn                                                                                       675     - #            680     - #            685                  - -      Gly Ser Leu Asp Thr Phe Leu Lys - # Lys Asn Asp Gly Gln Phe        Thr Val                                                                                   690         - #        695         - #        700                      - -      Ile Gln Leu Val Gly Met Leu Arg - # Gly Ile Ser Ala Gly Met        Lys Tyr                                                                               705             - #    710             - #    715             - #         720                                                                            - -      Leu Ser Asp Met Gly Tyr Val His - # Arg Asp Leu Ala Ala Arg         Asn Ile                                                                                            - #   725              - #   730              - #          735                                                                               - -      Leu Ile Asn Ser Asn Leu Val Cys - # Lys Val Ser Asp Phe Gly        Leu Ser                                                                                           740 - #                745 - #                750             - -      Arg Val Leu Glu Asp Asp Pro Glu - # Ala Ala Tyr Thr Thr Arg         Gly Gly                                                                                       755     - #            760     - #            765                  - -      Lys Ile Pro Ile Arg Trp Thr Ala - # Pro Glu Ala Ile Ala Phe        Arg Lys                                                                                   770         - #        775         - #        780                      - -      Phe Thr Ser Ala Ser Asp Val Trp - # Ser Tyr Gly Ile Val Met        Trp Glu                                                                               785             - #    790             - #    795             - #         800                                                                            - -      Val Val Ser Tyr Gly Glu Arg Pro - # Tyr Trp Glu Met Thr Asn         Gln Asp                                                                                            - #   805              - #   810              - #          815                                                                               - -      Val Ile Lys Ala Val Glu Glu Gly - # Tyr Arg Leu Pro Ser Pro        Met Asp                                                                                           820 - #                825 - #                830             - -      Cys Pro Ala Ala Leu Tyr Gln Leu - # Met Leu Asp Cys Trp Gln         Lys Glu                                                                                       835     - #            840     - #            845                  - -      Arg Asn Ser Arg Pro Lys Phe Asp - # Glu Ile Val Asn Met Leu        Asp Lys                                                                                   850         - #        855         - #        860                      - -      Leu Ile Arg Asn Pro Ser Ser Leu - # Lys Thr Leu Val Asn Ala        Ser Cys                                                                               865             - #    870             - #    875             - #         880                                                                            - -      Arg Val Ser Asn Leu Leu Ala Glu - # His Ser Pro Leu Gly Ser         Gly Ala                                                                                            - #   885              - #   890              - #          895                                                                               - -      Tyr Arg Ser Val Gly Glu Trp Leu - # Glu Ala Ile Lys Met Gly        Arg Tyr                                                                                           900 - #                905 - #                910             - -      Thr Glu Ile Phe Met Glu Asn Gly - # Tyr Ser Ser Met Asp Ala         Val Ala                                                                                       915     - #            920     - #            925                  - -      Gln Val Thr Leu Glu Asp Leu Arg - # Arg Leu Gly Val Thr Leu        Val Gly                                                                                   930         - #        935         - #        940                      - -      His Gln Lys Lys Ile Met Asn Ser - # Leu Gln Glu Met Lys Val        Gln Leu                                                                               945             - #    950             - #    955             - #         960                                                                            - -      Val Asn Gly Met Val Pro Leu                                                            - #   965                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:31:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 33 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:31:                        - - GAATTCGTCG ACCCGGCGAA CCATGGCTGG GAT       - #                  - #              33                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:32:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 38 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:32:                        - - GAATTCTCTA GATTATCATG TGGAGTTAGC CCCATCTC      - #                       - #     38                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:33:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 59 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:33:                        - - TCGCCCTATT TTCGTGTCTC TTCGGGATTT GCGACGCTCT CCGGACCCTC CT -              #GGCCAGC      59                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:34:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 37 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:34:                        - - GAATTCTCTA GATTATCACT GGCTTTGATC GCTGGAT      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:35:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 60 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:35:                        - - GAATTCGTCG ACCCGGCGAA CCATGGCTGG GATTTTCTAT TTCGCCCTAT TT -              #TCGTGTCT     60                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:36:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 37 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: cDNA                                               - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:36:                        - - GAATTCTCTA GATTATCACT GGCTTTGATC GCTGGAT      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:37:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 18 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:37:                        - -      Met Ala Gly Ile Phe Tyr Phe Ala - # Leu Phe Ser Cys Leu Phe         Gly Ile                                                                               1             - #  5                - #   10               - #          15                                                                                - -      Cys Asp                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:38:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 13 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:38:                        - -      Cys Leu Glu Thr Gln Ser Lys Asn - # Gly Pro Val Pro Val                  1             - #  5                - #   10                               - -  - - (2) INFORMATION FOR SEQ ID NO:39:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 13 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:39:                        - -      Cys Arg Ala Gln Met Asn Gln Ile - # Gln Ser Val Glu Val                   1             - #  5                - #   10                               - -  - - (2) INFORMATION FOR SEQ ID NO:40:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 13 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:40:                        - -      Cys Met Lys Val Gln Leu Val Asn - # Gly Met Val Pro Leu                   1             - #  5                - #   10                               - -  - - (2) INFORMATION FOR SEQ ID NO:41:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 16 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:41:                        - -      Cys Met Arg Thr Gln Met Gln Gln - # Met His Gly Arg Met Val         Pro Val                                                                               1             - #  5                - #   10               - #          15                                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:42:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 13 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:42:                        - -      Cys Gln Met Leu His Leu His Gly - # Thr Gly Ile Gln Val                  1             - #  5                - #   10                               - -  - - (2) INFORMATION FOR SEQ ID NO:43:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 10 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:43:                        - -      Cys Cys Cys Gly Cys Thr Thr Ala - # Ala Gly                               1             - #  5                - #   10                             __________________________________________________________________________ 

What is claimed is:
 1. An isolated nucleic acid encoding a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 11, SEQ ID NO: 13 or SEQ ID NO: 17, or a fragment thereof comprising at least an extracellular domain, a transmembrane domain, or a cytoplasmic domain.
 2. A nucleic acid of claim 1 which is cDNA or synthetic DNA or RNA.
 3. A nucleic acid of claim 1 comprising the nucleic acid sequence as set forth in SEQ ID NO: 10, SEQ ID NO: 12, or SEQ ID NO:
 16. 4. A nucleic acid of claim 1 encoding a fragment comprising an EPH-like receptor extracellular domain wherein the EPH-like receptor is selected from the group consisting of HEK5, HEK7 and HEK11.
 5. A nucleic acid of claim 1 which comprises one or more codons preferred for expression in E. coli host cells.
 6. A nucleic acid of claim 1 which comprises one or more codons preferred for expression in mammalian cells.
 7. A nucleic acid encoding a chimeric protein, wherein the protein comprises a fragment of an EPH-like receptor selected from the group consisting of HEK5 having the amino acid sequence as set forth in SEQ ID NO: 11, HEK7having the amino acid sequence as set forth in SEQ ID NO: 13 and HEK11 having the amino acid sequence as set forth in SEQ ID NO: 17, fused to an amino acid sequence from a heterologous protein, wherein the fragment comprises at least an extracellular domain, a transmembrane domain, or a cytoplasmic domain.
 8. A nucleic acid of claim 7 wherein the fragment is an EPH-like receptor extracellular domain.
 9. A nucleic acid of claim 7 wherein the heterologous protein is a heterologous receptor cytoplasmic domain or an Ig protein domain.
 10. An expression vector comprising the nucleic acid of claim 1 or
 7. 11. A procaryotic or eucaryotic host cell stably transformed or transfected with the vector of claim
 10. 12. A method of producing a polypeptide comprising culturing the host cell of claim 11 under conditions that allow the host cell to express the polypeptide, and isolating the polypeptide so expressed.
 13. A nucleic acid encoding amino acids 6-524 as set forth in SEQ ID NO: 11, and optionally encoding an amino terminal methionyl residue.
 14. A nucleic acid encoding amino acids 1-547 as set forth in SEQ ID NO: 13, and optionally encoding an amino acid terminal methionyl residue.
 15. A nucleic acid encoding amino acids 23-553 as set forth in SEQ ID NO: 17, and optionally encoding an amino terminal methionyl residue. 